OBJECTIVETo investigate effect of Chaiqin Chengqi Decoction (, CQCQD) on changes of neuronal acetylcholine receptor alpha 7 (nAChRα7) of peritoneal macrophages in acute pancreatitis (AP).

METHODSEighteen Kunming mice were equally randomized into the control group, AP group and CQCQD treatment group. AP was induced by two intraperitoneal injections of 4 g/kg L-arginine at 1 h apart, while control mice received saline injections. At 72 h after the first injection of L-arginine, mice in the treatment group were intragastrically administered 0.1 mL/10 g CQCQD every 2 h for 3 times, whilst mice in the other two groups received the same amount of saline feeding. Mice were sacrificed by cervical dislocation 2 h after the last feeding of either CQCQD or saline. Peritoneal macrophages were collected for determination of nAChRα7 mRNA and protein expression. Serum was collected for detection of interleukin-6 (IL-6), IL-10 and acetylcholine (ACh) levels, and pancreas was for histopathology analysis.

RESULTSThe CQCQD treatment significantly ameliorated the severity of AP as evidenced by reducing the pancreatic histopathology score (4.5±0.5 vs. 6.2±1.7, P<0.05) and the serum IL-6 levels (1228.3±419.2 pg/mL vs. 1589.6±337.3 pg/mL, P<0.05). The mRNA and protein expression of nAChRα7 of the peritoneal macrophages in the AP group were similar to the control group (P>0.05), but were significantly up-regulated after the CQCQD treatment (P<0.05). The serum ACh levels in the AP group were significantly lower than those in the control group (3.1±0.6 μg/mL vs 4.8±0.7 μg/mL P<0.05), but were significantly increased after the CQCQD treatment (5.6±1.5 μg/mL vs 3.1±0.6 μg/mL, P<0.05).

CONCLUSIONCQCQD is protective against L-arginine-induced AP through mechanisms involving nAChRα7 of peritoneal macrophages.

Acetylcholine ; pharmacology ; Acute Disease ; Animals ; Blotting, Western ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Macrophages, Peritoneal ; drug effects ; metabolism ; pathology ; Mice ; Neurons ; drug effects ; metabolism ; Pancreas ; drug effects ; pathology ; Pancreatitis ; blood ; drug therapy ; pathology ; RNA, Messenger ; genetics ; metabolism ; alpha7 Nicotinic Acetylcholine Receptor ; genetics ; metabolism

OBJECTIVETo study the effects and immunoregulation mechanism of the traditional Mongolian medicine Wuweifengshi capsule on adjuvant arthritis (AA).

METHODWister rats were divided into several groups: normal group, AA model group, Wuweifengshi capsule groups (with low, moderate, high dose of 0.2, 0.4, 0.8 g x kg(-1) x d(-1) respectively), and Zhonglun-5 group (original dose of 1.68 g x kg(-1) x d(-1)). The edema degree, the level of IL-1beta, TNF-alpha, PGE2, NO and MDA and the activity of SOD in serum were detected. Through cell culture, the effects of the medicine on AA rat's splenic cell's multiplication capacity were studied. The influence of celiac macrophage cell culture fluid of AA rats' on C57BL/6J mice thymic cell multiplication capacity under the medicine was evaluated.

RESULTWuweifengshi capsule showed an inhibiting function on the level of IL-1beta, TNF-alpha, PGE2, NO and increased the activity of SOD in serum, but showed no significant influence on MDA. It also inhibited the AA rat's splenic cell's multiplication capacity and the influence of celiac macrophage cell culture fluid of AA rat's on C57BL/6J mice thymic cell multiplication capacity.

CONCLUSIONThe anti-AA effect of Wuweifengshi capsule is possibly due to its inhibition of relevant cytokines and its adjustment of corresponding enzyme's activity and immunization organ's cell multiplication capacity.

Animals ; Arthritis, Experimental ; drug therapy ; immunology ; metabolism ; pathology ; Capsules ; Dehydroascorbic Acid ; analogs & derivatives ; blood ; Dinoprostone ; metabolism ; Disease Models, Animal ; Edema ; drug therapy ; Female ; Interleukin-1beta ; metabolism ; Lymphocytes ; immunology ; metabolism ; Macrophages, Peritoneal ; metabolism ; Male ; Medicine, Mongolian Traditional ; Mice ; Nitric Oxide ; metabolism ; Rats ; Spleen ; cytology ; metabolism ; Superoxide Dismutase ; blood ; Tumor Necrosis Factor-alpha ; metabolism

Pannexin-1 (Panx1) forms nonselective large channel in cell plasma membrane and has been shown to be associated with NLRP3 inflammasome activation, ATP release and phagocytes recruitment. In the current study, by manipulation of Panx1 expression in human myeloid cells and application of Panx1 deficient mice, we failed to find a correlation between Panx1 and NLRP3 inflammasome activation, although an interaction between these two proteins was evident. However, in thioglycollate induced peritonitis, Panx1 deficient mice showed much more phagocytes infiltration. Further analyses showed that mice deficient for Panx1 exhibited enlarged F4/80(low)Gr1(-)Ly6C(-)cell population in the peritonea. Our study thus reveals an important role for Panx1 in regulation of peritoneal cell population and peritonitis development.
Animals ; Carrier Proteins ; metabolism ; Cell Line ; Connexins ; antagonists & inhibitors ; deficiency ; genetics ; metabolism ; HEK293 Cells ; Humans ; Inflammasomes ; metabolism ; Macrophages ; cytology ; metabolism ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nerve Tissue Proteins ; antagonists & inhibitors ; deficiency ; genetics ; metabolism ; Peritoneal Cavity ; cytology ; Peritonitis ; chemically induced ; metabolism ; pathology ; RNA Interference ; RNA, Small Interfering ; metabolism ; Thioglycolates ; toxicity

OBJECTIVETo evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl4 intoxicated Swiss albino mice.

METHODSFirst group of mice (n=5) received CCl4 treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl4 (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups.

RESULTSThe result of present study suggested that CCl4 administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl4 intoxicated mice. Apart from damaging the liver system, CCl4 also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of CCl4 intoxicated mice.

CONCLUSIONSIn conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Carbon Tetrachloride ; toxicity ; Cell Adhesion ; drug effects ; immunology ; Curcuma ; chemistry ; Cytotoxicity, Immunologic ; drug effects ; Immunologic Factors ; pharmacology ; Liver ; drug effects ; metabolism ; pathology ; Macrophages, Peritoneal ; drug effects ; immunology ; metabolism ; pathology ; Male ; Mice ; Nitric Oxide ; metabolism ; Peroxidase ; metabolism ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology

Plasma sphingomyelin (SM) has been shown to be an independent risk factor for coronary heart disease, and sphingomyelin synthase 2 (SMS2) contributes to de novo SM biosynthesis and plasma membrane SM levels. The aim of the present study is to evaluate the in vivo role of SMS2 deficiency in serum SM metabolism and atherosclerosis (AS) development. We used male SMS2 knockout (SMS2(-/-)) and C57BL/6J (wild-type, WT) mice as experimental and control groups, respectively. Each group was fed high-fat diet (1% cholesterol, 20% leaf fat), as well as bile salt for accelerating the atherosclerotic formation. After three months of feeding, the mice were killed to observe aortic arches and oil red-stained longitudinal sections of thoracoabdominal aortae. Fasting blood samples were taken from the tail vein before and after high-fat diet, and the serum lipid and SM levels were measured by using kits and enzymatic method respectively. Western blot was used to analyze the contents of nuclear factor-kappaB (NFkappaB) p65 subunit in peritoneal macrophages stimulated with lipopolysaccharide (LPS) after high-fat diet. The results showed that after high-fat diet, SMS2(-/-) mice presented decreased atherosclerotic lesions in aortic arch and thoracoabdominal aorta compared with WT mice. Regardless of whether high-fat diet were given or not, SMS2(-/-) mice showed a significant decrease in serum SM level (P<0.05), but no significant changes in serum lipid levels, compared with WT mice. The expressions of NFkappaB p65 were attenuated in macrophages from SMS2(-/-) mice in response to LPS stimulation compared with those of the WT mice. These results suggest that SMS2 deficiency decreases AS and inhibits inflammation in mice. Thus, SMS2 deficiency may be a potential therapeutic strategy.
Animals ; Aorta ; pathology ; Atherosclerosis ; metabolism ; physiopathology ; prevention & control ; Diet, High-Fat ; Dietary Fats ; administration & dosage ; Gene Knockout Techniques ; Inflammation ; prevention & control ; Macrophages, Peritoneal ; enzymology ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B ; metabolism ; Sphingomyelins ; blood ; Transferases (Other Substituted Phosphate Groups) ; genetics

This study is to investigate the therapeutic effect of syringin on adjuvant arthritis (AA) in rats and its mechanisms. Complete Freund's adjuvant (FCA) was used to induce AA in rats. Secondary paw swelling of AA rats was measured with volume meter. Pain response and polyarthritis index were scored. Meanwhile, splenic lymphocyte proliferation response induced by concanavalin A (ConA) or lipopolysaccharide (LPS) was examined with MTT assay. IL-2 production of splenic lymphocytes and IL-1 beta, TNF-alpha production of peritoneal macrophage (PM phi) were estimated by enzyme linked immunosorbent assay (ELISA). The secondary inflammation of AA rats appeared on the 14th day after injection of FCA. Syringin and tripterygium glycosides (TG) were given by intragastric administration for 16 days from the 14th day. Treatment of AA rats with syringin and TG from the 22th day significantly attenuated the secondary hind paw swelling, as well as relieved the pain response and the polyarthritic symptoms of the whole body as compared with that of the AA model group. The suppressed lymphocyte proliferation and IL-2 production of splenic lymphocytes in AA rats were reversed by treatment with syringin. Meanwhile, syringin remarkably down-regulated IL-1 beta, TNF-alpha productions from PM phi. These results indicate that anti-inflammatory effects of syringin on AA rats are mediated by modulating the immune function of abnormal cells and the balance of cytokines.
Animals ; Anti-Inflammatory Agents ; isolation & purification ; pharmacology ; Arthritis, Experimental ; chemically induced ; drug therapy ; metabolism ; pathology ; Cell Proliferation ; drug effects ; Eleutherococcus ; chemistry ; Freund's Adjuvant ; Glucosides ; isolation & purification ; pharmacology ; Interleukin-1beta ; metabolism ; Interleukin-2 ; metabolism ; Lymphocytes ; metabolism ; pathology ; Macrophages, Peritoneal ; metabolism ; Male ; Phenylpropionates ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Spleen ; pathology ; Tumor Necrosis Factor-alpha ; metabolism

As a part of our ongoing search for a safe and efficient anti-tumor vaccine, we attempted to determine whether the molecular nature of certain tumor antigens would influence immune responses against tumor cells. As compared with freeze-thawed or formaldehyde-fixed tumor antigens, heat-denatured tumor antigens elicited profound anti-tumor immune responses and greatly inhibited the growth of live tumor cells. The heat-denatured tumor antigens induced a substantial increase in the anti-tumor CTL response in the absence of any adjuvant material. This response appears to be initiated by strong activation of the antigen-presenting cells, which may recognize heat-denatured protein antigens. Upon recognition of the heat-denatured tumor antigens, macrophages and dendritic cells were found to acutely upregulate the expression of co-stimulatory molecules such as B7.2, as well as the secretion of inflammatory cytokines such as IL-12 and TNF-alpha. The results of this study indicate that heat-denatured tumor extracts might elicit protective anti-tumor adaptive immune responses and also raise the possibility that a safe and efficient adjuvant-free tumor vaccine might be developed in conjunction with a dendritic cell-based tumor vaccine.
Adjuvants, Immunologic ; Animals ; Antibodies, Neoplasm/immunology ; Antibody Specificity/immunology ; Antigens, Neoplasm/immunology ; Cancer Vaccines/*immunology ; Cell Line, Tumor ; Cell Proliferation ; Cytokines/biosynthesis ; Cytotoxicity, Immunologic/immunology ; Dendritic Cells/immunology ; *Hot Temperature ; Immunity, Cellular/immunology ; Immunization ; Immunologic Memory/immunology ; Macrophages, Peritoneal/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasms/*immunology/*pathology ; Survival Analysis ; T-Lymphocytes, Cytotoxic/immunology

OBJECTIVETo investigate the effects of SiO(2) on the expression of alpha-smooth muscle actin (alpha-SMA) in human lung fibroblasts in vitro and vivo.

METHODSThe experimental group comprised 32 rats while 32 rats were included in the control. In vivo, the expression of alpha-SMA in lung tissues of rats exposed to SiO(2), the supernate of RAW264.7 cells, SiO(2) and the growth factor beta(1) (TGF-beta(1)) were investigated, respectively.

RESULTS(1) alpha-SMA positive myofibroblasts appeared in the lung tissues of the 28th day groups exposed to SiO(2). (2) The expression of alpha-SMA in HLF-02 cells was unregulated by TGF-beta(1) and supernate of RAW264.7 cells exposed to SiO(2). (3) The expression of alpha-SMA in HLF-02 cells was not induced by SiO(2).

CONCLUSIONMyofibroblasts related to silicosis, and the appearance of myofibroblasts (in vitro) are independent on direct stimulation by SiO(2), but related to the mediator (TGF-beta(1)) secreted by SiO(2) stimulated macrophages.

Actins ; biosynthesis ; genetics ; Animals ; Cells, Cultured ; Fibroblasts ; drug effects ; metabolism ; Lung ; cytology ; metabolism ; Macrophages, Peritoneal ; drug effects ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; pharmacology ; Silicosis ; metabolism ; pathology ; Transforming Growth Factor beta1 ; pharmacology

OBJECTIVETo observe the influences of FVP1 on both curative and negative effects of CTX.

METHODThe present study included two parts of experiments. In the part 1, 0.2 mL of 1 x 10(7) mL(-1) of S180 cells were inoculated in the subcutaneous layer of the right armpit of mice. All the mice were randomly divided into 3 groups: control group, in which mice were given with normal saline in 10 consecutive days, CTX group, in which mice were injected with 30 mg of CTX in the first and third days and saline in the other 8 days during the 10 consecutive days of treatment, and FVP1 and CTX group, in which the mice were injected with 30 mg x kg(-1) of CTX in the first and third days and FVP1 at 10 mg x kg(-1) in all 10 consecutive days of treatment. After above 10-day treatment , all the mice were killed and the tumor body was taken out and weighed to calculate the inhibiting rates on tumor. In the part 2 of experiments all the mice were divided into 3 groups: Normal control group, in which mice were not treated with any drugs, CTX-induced model group of inhibiting immune system, in which mice were injected with CTX at dose of 10 mg x kg(-1) in first two days and saline in the following 7 days; and small-, meddle-and large-dosage of FVP1 groups, in which mice were injected with CTX at the same dose as above in first two days and FVP1 intraperitoneally at 5, 10 and 20 mg x kg(-1) respectively in the following 7 days. CTX group was regarded as the control model. After the treatment, the peripheral white cells, thymus index, spleen index, the phagocytic power of macrophage of abdominal cavity, lymphocyte trastation rate and the activity of NK cell were detected.

RESULT(DFVP1 plus small dose of CTX obviously enhanced the inhibiting rate of CTX on tumor in the mice inoculated with S180 cells. (2) FVP1 at the different dose obviously antagozized CTX-induced leucopenia, atrophy, reduction of the phagocytic power of macrophage in abdominal cavity and restored the function of lymphocyte translation and the activity of NK cells.

CONCLUSIONFPV1 could enhance the curative effect of CTX in depressing tumor and attenuate the negative effect of CTX in inhibiting the function of immune system.

Agaricales ; chemistry ; Animals ; Antineoplastic Agents, Alkylating ; adverse effects ; pharmacology ; Cell Line, Tumor ; Cyclophosphamide ; adverse effects ; pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Killer Cells, Natural ; drug effects ; Leukopenia ; chemically induced ; Lymphocyte Activation ; drug effects ; Macrophages, Peritoneal ; physiology ; Mice ; Neoplasm Transplantation ; Phagocytosis ; drug effects ; Polysaccharides ; isolation & purification ; pharmacology ; Random Allocation ; Sarcoma 180 ; pathology

OBJECTIVETo study the adjustment of Xianggui pill on the cytokine of endometriosis model rat, and investigate the mechanism of Xianggui pill on the treatment of endometriosis.

METHODTo set up endometriosis model by rat self-endometria transplantation, drench sodium chloride, Xianggui pill elixation or Danazol after grouping, and to detect the contents of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) by ELISA.

RESULTThe contents of IL-8, TNF-alpha in the peripheral blood and peritoneal fluid of model group were higher than that of the blank group; The quality of allotopia growth intima tissue, the quantity of macrophage in peritoneal fluid and the contents of IL-8, TNF-alpha in the Xianggui pill group and Danazol group were all lower than those of the model group; but there was no significant difference of each target between the Xianggui pill group and Danazol group.

CONCLUSIONXianggui pill can restrain significantly the growth of allotopia intima tissue, and has apparently adjustment to the cytokine.

Animals ; Cell Count ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endometriosis ; blood ; immunology ; metabolism ; Female ; Interleukin-8 ; blood ; metabolism ; Macrophages, Peritoneal ; metabolism ; pathology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism