CN108815198A - Purposes of the Lyopgized Nocardia rubra-cell Wall Skeleton as macrophage proliferation promotor - Google Patents
Purposes of the Lyopgized Nocardia rubra-cell Wall Skeleton as macrophage proliferation promotor Download PDFInfo
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Abstract
Purposes the present invention relates to Lyopgized Nocardia rubra-cell Wall Skeleton as macrophage proliferation promotor, Macrophage Surface functional molecular MHC-II, CD86, CD80, TLR4 expression promotor, macrophage intracellular reactive oxygen species generation generation promotor, macrophage TNF-α, IL-6, IL-12p40, IL-1 β, IFN-β expression promotor, macrophage IL-10 expression inhibiting agent or macrophage killing ovarian cancer cell promotor.
Description
Technical field
The invention belongs to field of medicaments, and in particular to Lyopgized Nocardia rubra-cell Wall Skeleton promotes as macrophage proliferation
The purposes of agent.
Background technique
Nocard's bacillus be it is polymorphic, have that Nocardia is spherical, rod-shaped, Filamentous, thallus size 0.6 × (3~4) micron,
Without motion, some strains are in weak acid-resisting, and obligate aerobic, nutritional requirement is general.Have after being cultivated 3 days on plain agar plate
Visible colonies, bacterium colony projection after 7~10 days, after aerial hyphae is formed, surface is in villiform.Bacterium colony not of the same race has yellow, orange, red
Or the secondary colour of these pigments.G+C gram molecule content in DNA is 60~72%.It is mostly saprophytic bacteria, is present in soil.
Nocardia rubra (Nocardiarubra) is one such actinomyces.Nocardia rubra thallus is fermented, cell is broken
Lyopgized Nocardia rubra-cell Wall Skeleton (hereinafter referred to as Nr-CWS or N-CWS) can be made after broken, proteasome degradation.
Summary of the invention
Present invention discover that Lyopgized Nocardia rubra-cell Wall Skeleton can promote macrophage proliferation, promote Macrophage Surface
The expression of functional molecular MHC-II, CD86, CD80, TLR4, promote macrophage at the generation for promoting macrophage intracellular reactive oxygen species generation
TNF-α, IL-6, IL-12p40, IL-1 β, the expression of IFN-β, the expression of inhibition macrophage IL-10 and promotion macrophage are thin
Born of the same parents kill ovarian cancer cell, and then complete the present invention.
According to an aspect of the present invention, it is huge for promoting in preparation to provide Lyopgized Nocardia rubra-cell Wall Skeleton by the present invention
Purposes in the drug of phagocyte proliferation.According to the present invention, the drug can by promote macrophage proliferation treatment with it is huge
The relevant disease of phagocyte, including but not limited to：Such as body local tissue infection caused by the pathogenic microorganism of virus etc. or
Lesion and autoimmune disease.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton as non-treatment purpose
Macrophage proliferation promotor purposes.According to the present invention, described " non-treatment purpose " for example promotes macrophage in vitro
Proliferation.
According to another aspect of the present invention, the present invention provides a kind of external method for promoting macrophage proliferation, wherein
Give the macrophage Lyopgized Nocardia rubra-cell Wall Skeleton of in vitro culture.It is preferred that Lyopgized Nocardia rubra-cell Wall Skeleton is dense
Degree is 1-60 μ g/ml, further preferred 5-50 μ g/ml, more preferable 10-40 μ g/ml.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton in preparation for promoting
Purposes in the drug of Macrophage Surface functional molecular MHC-II, CD86, CD80 or TLR4 expression.According to the present invention, described
Drug can be by promoting Macrophage Surface functional molecular MHC-II, CD86, CD80 or TLR4 expression treatment and macrophage
Relevant disease, including but not limited to：Such as body local tissue infection or lesion caused by the pathogenic microorganism of virus etc., with
And autoimmune disease.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton as non-treatment purpose
Macrophage Surface functional molecular MHC-II, CD86, CD80 or TLR4 expression promotor purposes.According to the present invention, described
" non-treatment purpose " for example promotes Macrophage Surface functional molecular MHC-II, CD86, CD80 or TLR4 expression in vitro.
According to another aspect of the present invention, the present invention provides a kind of external promotion Macrophage Surface functional molecular MHC-
The method of II, CD86, CD80 or TLR4 expression, wherein give the macrophage nocardia rubracell wall bone of in vitro culture
Frame.It is preferred that the concentration of Lyopgized Nocardia rubra-cell Wall Skeleton is 1-60 μ g/ml, further preferred 5-50 μ g/ml, more preferable 10-
40μg/ml。
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton in preparation for promoting
The purposes in drug that macrophage intracellular reactive oxygen species generation generates.According to the present invention, the drug can be by promoting macrophage
Intracellular reactive oxygen species generation, which generates, treats disease relevant to macrophage, including but not limited to：Such as the pathogenic microorganism of virus etc. draws
The body local tissue infection or lesion and autoimmune disease risen.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton as non-treatment purpose
Macrophage intracellular reactive oxygen species generation generate promotor purposes.According to the present invention, described " non-treatment purpose " for example promotees in vitro
Into the generation of macrophage intracellular reactive oxygen species generation.
According to another aspect of the present invention, the present invention provides what the external promotion macrophage intracellular reactive oxygen species generation of one kind generated
Method, wherein give the macrophage Lyopgized Nocardia rubra-cell Wall Skeleton of in vitro culture.It is preferred that nocardia rubra cell
The concentration of wall skeleton is 1-60 μ g/ml, further preferred 5-50 μ g/ml, more preferable 10-40 μ g/ml.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton in preparation for promoting
The purposes in drug that macrophage TNF-α, IL-6, IL-12p40, IL-1 β or IFN-β are expressed.According to the present invention, the medicine
Object can be by promoting macrophage TNF-α, IL-6, IL-12p40, IL-1 β or IFN-β expression treatment related to macrophage
Disease, including but not limited to：Such as body local tissue infection or lesion caused by the pathogenic microorganism of virus etc., and from
Body immunity disease.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton as non-treatment purpose
Macrophage TNF-α, IL-6, IL-12p40, IL-1 β or IFN-β expression promotor purposes.According to the present invention, described " non-
Therapeutic purposes " for example promote macrophage TNF-α, IL-6, IL-12p40, IL-1 β or IFN-β expression in vitro.
According to another aspect of the present invention, the present invention provides a kind of external promotion macrophage TNF-α, IL-6, IL-
12p40, IL-1 β or the method for IFN-β expression, wherein give the macrophage nocardia rubracell wall bone of in vitro culture
Frame.It is preferred that the concentration of Lyopgized Nocardia rubra-cell Wall Skeleton is 1-60 μ g/ml, further preferred 5-50 μ g/ml, more preferable 10-
40μg/ml。
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton in preparation for inhibiting
Purposes in the drug of macrophage IL-10 expression.According to the present invention, the drug can be by inhibiting macrophage IL-10
Expression treatment disease relevant to macrophage, including but not limited to：Such as body office caused by the pathogenic microorganism of virus etc.
Portion's tissue infection or lesion and autoimmune disease.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton as non-treatment purpose
Macrophage IL-10 expression inhibiting agent purposes.According to the present invention, described " non-treatment purpose " for example inhibits macrophage in vitro
Cell IL-10 expression.
According to another aspect of the present invention, the present invention provides a kind of external method for inhibiting macrophage IL-10 expression,
Wherein, the macrophage Lyopgized Nocardia rubra-cell Wall Skeleton of in vitro culture is given.It is preferred that Lyopgized Nocardia rubra-cell Wall Skeleton
Concentration be 1-60 μ g/ml, further preferred 5-50 μ g/ml, more preferable 10-40 μ g/ml.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton in preparation for treating
Purposes in the drug of oophoroma.
According to another aspect of the present invention, the present invention provides Lyopgized Nocardia rubra-cell Wall Skeleton as non-treatment purpose
Macrophage killing ovarian cancer cell promotor purposes.According to the present invention, described " non-treatment purpose " for example promotees in vitro
Ovarian cancer cell is killed into macrophage.
According to another aspect of the present invention, the present invention provides a kind of external side for promoting macrophage killing oophoroma
Method, wherein give the macrophage Lyopgized Nocardia rubra-cell Wall Skeleton of in vitro culture.It is preferred that nocardia rubracell wall
The concentration of skeleton is 1-60 μ g/ml, further preferred 5-50 μ g/ml, more preferable 10-40 μ g/ml.
It will be understood by those skilled in the art that Lyopgized Nocardia rubra-cell Wall Skeleton can it is commercially available or according to this field
The various methods known are prepared.It is preferred that nocardia rubra is that (it is micro- that it was preserved in China on 2 5th, 2002 to Nr-8206
Biological inoculum preservation administration committee common micro-organisms center, deposit number are CGMCC NO.0712).For example, can pass through by
DNA, DNA, RNA, protein, lipoid are removed after nocardia rubra fermentation, Lyopgized Nocardia rubra-cell Wall Skeleton is prepared,
Its principle active component is muramic acid, polysaccharide and mucopeptide, and molecular weight is about 2-20KD.
The present invention by experiment confirm for the first time Lyopgized Nocardia rubra-cell Wall Skeleton can promote macrophage proliferation, promote it is huge
The expression of phagocyte function of surface molecule MHC-II, CD86, CD80 or TLR4, the generation for promoting macrophage intracellular reactive oxygen species generation,
Promote macrophage TNF-α, IL-6, IL-12p40, IL-1 β or IFN-β expression, inhibit macrophage IL-10 expression, with
And macrophage is promoted to kill ovarian cancer cell, so that Lyopgized Nocardia rubra-cell Wall Skeleton can be used to treat in vivo
Disease related with macrophage and oophoroma, and can be used to promote macrophage proliferation in vitro, promote macrophage thin
The expression of cellular surface functional molecular MHC-II, CD86, CD80 or TLR4, promote the generation for promoting macrophage intracellular reactive oxygen species generation
Macrophage TNF-α, IL-6, IL-12p40, IL-1 β or IFN-β expression, inhibit the expression of macrophage IL-10 and promote
Ovarian cancer cell is killed into macrophage.
Detailed description of the invention
Fig. 1 Lyopgized Nocardia rubra-cell Wall Skeleton promotes macrophage proliferation
The interior promotion Macrophage Surface functional molecular MHC-II, CD86 of Fig. 2 Lyopgized Nocardia rubra-cell Wall Skeleton body,
The expression of CD80 and TLR4：Fig. 2A is streaming figure；Fig. 2 B is MHC-II, CD86, CD80 and TLR4 expression comparison
Fig. 3 Lyopgized Nocardia rubra-cell Wall Skeleton promote in vitro Macrophage Surface functional molecular MHC-II, CD86,
The expression of CD80 and TLR4
Promote the generation of macrophage intracellular reactive oxygen species generation in Fig. 4 Lyopgized Nocardia rubra-cell Wall Skeleton body
Fig. 5 Lyopgized Nocardia rubra-cell Wall Skeleton promotes the generation of macrophage intracellular reactive oxygen species generation in vitro
Fig. 6 Lyopgized Nocardia rubra-cell Wall Skeleton promotes macrophage TNF-α, IL-6, IL-12p40, IL-1 β and IFN-
The expression of β and the expression for inhibiting IL-10
Fig. 7 Lyopgized Nocardia rubra-cell Wall Skeleton promotes macrophage to kill ovarian cancer cell
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.Furthermore, it is to be understood that after having read documented content of the invention, this field skill
Art personnel can make various changes or modifications the present invention, and such equivalent forms equally fall within limited range of the present invention.
Embodiment 1.Nr-CWS promotes macrophage proliferation
Mouse macrophage strain Raw264.7 cell presses 2 × 105/ ml cell density is inoculated with 96 orifice plates, every 100 μ l of hole.It will
Macrophage is in 37 DEG C, 5%CO2Incubator in cultivate 2 hours it is adherent to cell, experimental group addition culture solution dissolves dense
Degree is respectively Nr-CWS (Liaoning Ge Ruishitesheng of 5 μ g/ml, 10 μ g/ml, 20 μ g/ml, 40 μ g/ml, 60 μ g/ml, 80 μ g/ml
Object pharmaceutical Co. Ltd, similarly hereinafter), every 100 μ l of hole, each concentration sets 3 multiple holes.RPMI 1640 is added in zeroing hole, that is, control group
Culture solution, every 100 μ l of hole, if 3 multiple holes.In 37 DEG C, 5%CO2Incubator in cultivate 12 hours and 24 hours, be inverted it is micro-
Microscopic observation cell quantity.10 μ l CCK-8 are added in every hole, continue culture 4 hours.After terminating culture, in enzyme-linked immunosorbent assay instrument
The absorbance in each hole, reference wavelength 600nm are measured at OD450nm.
As a result it is shown (see Fig. 1), Nr-CWS is when concentration is 20 μ g/ml, 40 μ g/ml, 60 μ g/ml, 80 μ g/ml, processing
After macrophage 24 hours, macrophage proliferation significantly increases (* * p compared with the control group<It 0.01) is, and in concentration 60 μ g/ml
Shi Shenggao is the most significant.
The expression of embodiment 2.Nr-CWS promotion Macrophage Surface functional molecular MHC-II, CD86, CD80 and TLR4
1. experiment in vivo
20 mouse are randomly divided into 4 groups, every group 5, difference intraperitoneal injection of saline (control group) is molten with culture solution
The Nr-CWS of the 25 μ g/ml (low concentration group), 50 μ g/ml (middle concentration group) and 100 μ g/ml (high concentration group) that solve, dosage are
1ml, the PBS of every group of mouse peritoneal injection 5ml, gently rubs 3min after 3 days, and abdominal cut skin exposes peritonaeum, acquires whole abdomens
Chamber liquid, 1500rpm/min are centrifuged 5min, abandon supernatant, and cell is resuspended with the RPMI1640 culture solution of 3ml respectively.Take 1 × 106Institute
Macrophage is obtained, PBS is washed 1 time, and cell is resuspended with 100 μ l PBS.Rabbit anti-mouse F4/80 antibody, the 1 μ g of 1 μ g PE label is added
The rabbit-anti of the rabbit anti-mouse CD80 antibody of APC label, the rabbit anti-mouse CD86 antibody of 1 μ g FITC label, 1 μ g PerCP label
The rabbit anti-mouse TLR4 antibody of mouse MHC-II antibody, 1 μ g PE-CY7 label, 4 DEG C are protected from light incubation 30 minutes.According to experimental group
The fluorescent marker of antibody selects the rabbit anti-mouse IgG2b Isotype antibody of each fluorescent marker as negative control respectively, not with antibody
The macrophage of effect is as a control group.Free antibody is washed away with PBS, and cell is resuspended with the PBS of 0.3ml.It is thin with streaming
The expression of born of the same parents instrument FACS Calibur (BD, USA) the detection surface macrophage (F4/80+) MHC-II, CD80, CD86 and TLR4.
As a result it is shown (see Fig. 2A and Fig. 2 B), after the Nr-CWS that concentration is 25 μ g/ml handles mouse, mouse macrophage table
The expression of face functional molecular MHC-II, CD86, CD80 significantly increase (* p compared with the control group<0.05 or * * p<0.01)；Concentration
After handling mouse for the Nr-CWS of 50 μ g/ml and 100 μ g/ml, mouse macrophage function of surface molecule MHC-II, CD86,
CD80, TLR4 expression significantly increase (* * p compared with the control group<0.01).
2. experiment in vitro
Mouse macrophage strain Raw264.7 cell presses 1 × 105/ ml cell density is inoculated with 24 orifice plates, every 300 μ l of hole.It is real
Nr-CWS, the every 100 μ l of hole that group addition is respectively 20 μ g/ml, 40 μ g/ml, 60 μ g/ml with the concentration that culture solution dissolves are tested, often
A concentration sets 3 multiple holes.Equivalent PBS is added in control group, if 3 multiple holes.In 37 DEG C, 5%CO2Incubator in culture it is 24 small
When, it discards supernatant, is digested with 0.5% pancreatin and obtain individual cells suspension, adjustment cell concentration is 5 × 105/ ml carries out streaming
Antibody dyeing, as previously described.Free antibody is washed away with PBS, and cell is resuspended with the PBS of 0.3ml.With flow cytometer FACS
The expression of Calibur (BD, USA) the detection surface macrophage (F4/80+) MHC-II, CD80, CD86 and TLR4.
As a result it being shown (see Fig. 3), Nr-CWS is when concentration is 20 μ g/ml, after processing macrophage 24 hours, macrophage
The expression of function of surface molecule MHC-II, CD86, CD80, TLR4 significantly increase (* p compared with the control group<0.05 or * * p<
0.01)；Nr-CWS is when concentration is 40 μ g/ml and 60 μ g/ml, after processing macrophage 24 hours, Macrophage Surface function
The expression of molecule MHC-II, CD86, CD80, TLR4 significantly increase (* * p compared with the control group<0.01).
Embodiment 3.Nr-CWS promotes active oxygen in macrophage
1. experiment in vivo
20 mouse are randomly divided into 4 groups, every group 5, difference intraperitoneal injection of saline (control group) is molten with culture solution
The Nr-CWS of the 25 μ g/ml (low concentration group), 50 μ g/ml (middle concentration group) and 100 μ g/ml (high concentration group) that solve, dosage are
1ml, the PBS of every group of mouse peritoneal injection 5ml, gently rubs 3min after 3 days, and abdominal cut skin exposes peritonaeum, acquires whole abdomens
Chamber liquid, 1500rpm/min are centrifuged 5min, abandon supernatant, cell are resuspended with the RPMI1640 culture solution of 3ml respectively, by 1 × 106/ml
Cell density is inoculated with 6 orifice plates, every 100 μ l of hole.With serum-free medium according to 1:1000 dilution DCFH-DA, keep its final concentration of
10μmol/L.Cell culture fluid is removed, the DCFH-DA diluted is added, sufficiently covers cell.In 37 DEG C, 5%CO2Culture
It is cultivated 20 minutes in case.Cell is washed three times with serum-free cell culture medium, and intracellular DCFH- is not entered with abundant removal
DA.It is excited with 488nm, carries out flow cytometer showed.
As a result (see Fig. 4) show, concentration be 25 μ g/ml Nr-CWS handle mouse after, in mouse macrophage ROS with it is right
Apparent increase (* p is compared according to group<0.05)；After the Nr-CWS that concentration is 50 μ g/ml and 100 μ g/ml handles mouse, mouse macrophage
Intracellular ROS significantly increases (* * p compared with the control group<0.01).
2. experiment in vitro
Mouse macrophage strain Raw264.7 cell presses 1 × 105/ ml cell density is inoculated with 6 orifice plates, every 300 μ l of hole.Experiment
Group addition is respectively Nr-CWS, the every 100 μ l of hole of 20 μ g/ml, 40 μ g/ml, 60 μ g/ml with the concentration that culture solution dissolves, each
Concentration sets 3 multiple holes.Equivalent PBS is added in control group, if 3 multiple holes.In 37 DEG C, 5%CO2Incubator in cultivate 24 hours.
With serum-free medium according to 1:1000 dilution DCFH-DA, make its final concentration of 10 μm of ol/L.Cell culture fluid is removed, is added
The DCFH-DA diluted, sufficiently covers cell.In 37 DEG C, 5%CcO2Incubator in cultivate 20 minutes.Use serum-free cell
Culture solution washs cell three times, does not enter intracellular DCFH-DA with abundant removal.It is excited with 488nm, carries out flow cytometer showed.
As a result it being shown (see Fig. 5), Nr-CWS is when concentration is 20 μ g/ml, after processing mouse macrophage 24 hours, mouse
ROS there was no significant difference compared with the control group (p in macrophage>0.05)；Nr-CWS is 40 μ g/ml and 60 μ g/ml in concentration
When, after processing mouse macrophage 24 hours, ROS significantly increases (* * p compared with the control group in mouse macrophage<
0.01)。
Embodiment 4.Nr-CWS promotes the expression of macrophage TNF-α, IL-6, IL-12p40, IL-1 β, IFN-β, inhibits
The expression of IL-10
Mouse macrophage strain Raw264.7 cell presses 1 × 105/ ml cell density is inoculated with 96 orifice plates, every 100 μ l of hole.It is real
Nr-CWS, the every 100 μ l of hole that group addition is respectively 20 μ g/ml, 40 μ g/ml, 60 μ g/ml with the concentration that culture solution dissolves are tested, often
A concentration sets 3 multiple holes.Equivalent PBS is added in control group, if 3 multiple holes.In 37 DEG C, 5%CO2Incubator in culture it is 24 small
When, culture supernatant is taken, ELISA detects cytokine content.
As a result it being shown (see Fig. 6), Nr-CWS is when concentration is 20 μ g/ml, after processing mouse macrophage 24 hours, mouse
Expression of Macrophages IL-6 significantly increases (* * p compared with the control group<0.01)；Nr-CWS is 40 μ g/ml and 60 μ g/ml in concentration
When, after processing mouse macrophage 24 hours, mouse macrophage is expressed TNF-α, IL-6, IL-12p40 and IL-1 β and is compareed
Group increases (* p compared to significant<0.05 or * * p<0.01)；Nr-CWS handles mouse macrophage 24 when concentration is 60 μ g/ml
After hour, mouse macrophage expresses IFN-β and significantly increases (* * p compared with the control group<0.01) IL-10 and control group, are expressed
Compared to significant decrease (* p<0.05).
Embodiment 5.Nr-CWS promotes macrophage to kill ovarian cancer cell
Mouse macrophage strain Raw264.7 cell presses 1 × 105/ ml cell density is inoculated with 96 orifice plates, every 100 μ l of hole.It is real
Nr-CWS, the every 100 μ l of hole that group addition is respectively 20 μ g/ml, 40 μ g/ml, 60 μ g/ml with the concentration that culture solution dissolves are tested, often
A concentration sets 3 multiple holes.Equivalent PBS is added in control group, if 3 multiple holes.In 37 DEG C, 5%CO2Incubator in culture it is 24 small
When, it discards supernatant, is digested with 0.5% pancreatin and obtain individual cells suspension, adjustment cell concentration is 5 × 106/ml.Collect 5 × 105
U14 ovarian cancer cell, be resuspended with the PBS of 1mL.The macrophage of various concentration Nr-CWS stimulation is pressed with U14 ovarian cancer cell
According to ratio 1：10 96 orifice plates of inoculation, every 100 μ l of hole, if 3 multiple holes.Zeroing hole, that is, blank group addition culture solution, every 100 μ l of hole,
If 3 multiple holes.Control group is not with by the Nr-CWS macrophage stimulated and U14 ovarian cancer cell proportionally 1：10 96 holes of inoculation
Plate, every 100 μ l of hole, if 3 multiple holes.In 37 DEG C, 5%CO2Incubator in cultivate for 24 hours.The MTT solution of 20 μ l is added in every hole
(5mg/ml, i.e. 0.5%MTT) continues culture 4 hours.Culture is terminated, culture solution in hole is sucked.150ul dimethyl is added in every hole
Sulfoxide sets low-speed oscillation 10min on shaking table, dissolves crystal sufficiently.At enzyme-linked immunosorbent assay instrument OD490nm (570nm)
Measure the light absorption value in each hole.Cytotoxic activity (cell killing rate %) is calculated referring to following equation：
As a result it is shown (see Fig. 7), Nr-CWS handles mouse macrophage when concentration is 20 μ g/ml, 40 μ g/ml, 60 μ g/ml
After cell 24 hours, mouse macrophage kills ratio of outflow and significantly increases (* * p compared with the control group<0.01).
More than, embodiments of the present invention are illustrated.But the present invention is not limited to above embodiment.It is all
Within the spirit and principles in the present invention, any modification, equivalent substitution, improvement and etc. done should be included in guarantor of the invention
Within the scope of shield.
Claims (10)
1. Lyopgized Nocardia rubra-cell Wall Skeleton is preparing the purposes in the drug for promoting macrophage proliferation.
2. purposes of the Lyopgized Nocardia rubra-cell Wall Skeleton as the macrophage proliferation promotor of non-treatment purpose.
3. a kind of external method for promoting macrophage proliferation, wherein give the macrophage nocardia rubra of in vitro culture
Cell wall skeleton.It is preferred that the concentration of Lyopgized Nocardia rubra-cell Wall Skeleton be 1-60 μ g/ml, further preferred 5-50 μ g/ml,
More preferable 10-40 μ g/ml.
4. Lyopgized Nocardia rubra-cell Wall Skeleton preparation for promote Macrophage Surface functional molecular MHC-II, CD86,
CD80 or TLR4 expression or promotion macrophage intracellular reactive oxygen species generation generate or promote macrophage TNF-α, IL-6, IL-
Purposes in 12p40, IL-1 β or IFN-β expression or the drug for inhibiting macrophage IL-10 to express.
5. Lyopgized Nocardia rubra-cell Wall Skeleton as non-treatment purpose Macrophage Surface functional molecular MHC-II, CD86,
CD80 or TLR4 expression promotor or macrophage intracellular reactive oxygen species generation generate promotor or macrophage TNF-α, IL-6,
IL-12p40, IL-1 β or IFN-β expression promotor or the purposes of macrophage IL-10 expression inhibiting agent.
6. a kind of external promotion Macrophage Surface functional molecular MHC-II, CD86, CD80 or TLR4 are expressed or are promoted in vitro
Macrophage intracellular reactive oxygen species generation generates or external promotion macrophage TNF-α, IL-6, IL-12p40, IL-1 β or IFN-β table
The method for reaching or macrophage IL-10 being inhibited to express in vitro, wherein give the macrophage red promise Cattell of in vitro culture
Bacterium cell wall skeleton.It is preferred that the concentration of Lyopgized Nocardia rubra-cell Wall Skeleton is 1-60 μ g/ml, further preferred 5-50 μ g/
Ml, more preferable 10-40 μ g/ml.
7. Lyopgized Nocardia rubra-cell Wall Skeleton is preparing the purposes in the drug for treating oophoroma.
8. use of the Lyopgized Nocardia rubra-cell Wall Skeleton as the macrophage killing ovarian cancer cell promotor of non-treatment purpose
On the way.
9. a kind of external method for promoting macrophage killing oophoroma, wherein give the macrophage red promise of in vitro culture
Cattell bacterium cell wall skeleton.It is preferred that the concentration of Lyopgized Nocardia rubra-cell Wall Skeleton is 1-60 μ g/ml, further preferred 5-50 μ
G/ml, more preferable 10-40 μ g/ml.
10. purposes as claimed in any one of claims 1-9 wherein or method, wherein nocardia rubra Nr-8206.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110849851A (en) * | 2019-11-22 | 2020-02-28 | 辽宁省检验检测认证中心 | Novel method for rapidly evaluating immunity enhancement of medicine/health-care product based on flow cytometry fluorescent microsphere dual-standard method |
| WO2021147899A1 (en) * | 2020-01-21 | 2021-07-29 | 辽宁格瑞仕特生物制药有限公司 | Use of rhodococcus ruber cell wall skeleton in regenerative medicine |
| CN114402064A (en) * | 2020-01-21 | 2022-04-26 | 辽宁格瑞仕特生物制药有限公司 | Use of nocardia rubra cell wall skeleton in regenerative medicine |
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| CN1094288A (en) * | 1993-04-23 | 1994-11-02 | 福建省微生物研究所 | Utilize nocardia rubra to make the method for cell wall skeleton powder |
| CN103961693A (en) * | 2013-01-24 | 2014-08-06 | 熊慧 | Therapeutic vaccine for malignant tumors and composition thereof |
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| CN1094288A (en) * | 1993-04-23 | 1994-11-02 | 福建省微生物研究所 | Utilize nocardia rubra to make the method for cell wall skeleton powder |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110849851A (en) * | 2019-11-22 | 2020-02-28 | 辽宁省检验检测认证中心 | Novel method for rapidly evaluating immunity enhancement of medicine/health-care product based on flow cytometry fluorescent microsphere dual-standard method |
| WO2021147899A1 (en) * | 2020-01-21 | 2021-07-29 | 辽宁格瑞仕特生物制药有限公司 | Use of rhodococcus ruber cell wall skeleton in regenerative medicine |
| CN114402064A (en) * | 2020-01-21 | 2022-04-26 | 辽宁格瑞仕特生物制药有限公司 | Use of nocardia rubra cell wall skeleton in regenerative medicine |
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