ABSTRACT
Objective:To observe the Toll-like receptor 4(TLR4)and its negative regulating factorInterleukin-1 receptor-associated kinase-M(IRAK-M)in colonic mucosa of rats with experimental ulcerative colitis(UC), and to discuss the mechanism of the Chinese medicine Sishenwan. Method:The 90 Wistar rats were randomly divide into six groups, blank group, model group, sulfasalazine group(0.36 g·kg-1), Sishenwan low, medium and high-dose group(2.5, 5, 10 g·kg-1), 15 cases in each group. A rat model of UC was prepared by using a solution of trinitrobenzenesulfonic acid/ethano.The histopathological changes of colon were observed by hematoxylin-eosin (HE) staining. The contents of serum free triiodothyroid acid (FT3), serum free thyroxine (FT4), immunoglobulin (Ig) E and interleukin (IL)-2 were determined by radioimmunoassay. The activity of superoxide dismutase (SOD) in rat serum was determined by xanthine oxidation method. The activity of malondialdehyde (MDA) in serum of rats was determined by thiobarbituric acid (TBA) colorimetry. Result:Compared with blank group, intestinal mucosal injury score of rats in model group was significantly increased (PP3, FT4, IL-2 and SOD were significantly decreased (PPPPPP3, FT4, IL-2, and SOD contents were significantly increased (PPPPPConclusion:The unbalanced expressions of TLR4 and its negative regulating factor IRAK-M are connected with the pathogenesis of UC.Sishenwan can cure UC and control the expression of TLR4 and promote the expression of IRAK-M.
ABSTRACT
Objective:To observe whether pretreatment with Pam3CSK4,a TLR2 agonist,could decrease the inflammation response in kidney from mice with systemic MRSA infection,and to investigate the mechanism of the attenuation of inflammation with Pam3CSK4 pretreatment. Methods:BALB/c mice were pretreated with Pam3CSK4 (10 μg/100 μl/each mouse) or PBS via tail vein once daily for two consecutive days. All mice were infected with live MRSA (ATCC43300) at 2×107 CFU/each mouse (via tail vein) 24 h after the second treatment. The levels of cytokines in kidney were measured by ELISA and real-time PCR,respectively. The relative expression of TLR2,IRAKs etc. were detected by real-time PCR. Western blot was performed to detect the phosphorylation of NF-κB, the expression of IRAK-M and A20,respectively. Results:The level of TNF-α,IL-6,IL-1β,CCL3 and IFN-γ in renal tissue from mice pretreated with Pam3CSK4 was decreased significantly compared with that from PBS-treated mice,respectively. Pam3CSK4 pretreatment down-regulated the relative expression of TLR2, inhibited the expression of IRAK-1 and the phosphorylation of NF-κB post infection. The expression of IRAK-M,one of the negative regulators in TLRs signaling pathway was increased significantly in renal tissue from Pam3CSK4-treated mice post infection. Conclusion:Pam3CSK4 pretreatment attenuated the inflammation response in kidney from mice with systemic MRSA infection,and these attenuation is related with up-regulation of IRAK-M.
ABSTRACT
Objective:To observe whether pretreatment with Pam3CSK4,a TLR2 agonist,could decrease the inflammation response in kidney from mice with systemic MRSA infection,and to investigate the mechanism of the attenuation of inflammation with Pam3CSK4 pretreatment. Methods:BALB/c mice were pretreated with Pam3CSK4 (10 μg/100 μl/each mouse) or PBS via tail vein once daily for two consecutive days. All mice were infected with live MRSA (ATCC43300) at 2×107 CFU/each mouse (via tail vein) 24 h after the second treatment. The levels of cytokines in kidney were measured by ELISA and real-time PCR,respectively. The relative expression of TLR2,IRAKs etc. were detected by real-time PCR. Western blot was performed to detect the phosphorylation of NF-κB, the expression of IRAK-M and A20,respectively. Results:The level of TNF-α,IL-6,IL-1β,CCL3 and IFN-γ in renal tissue from mice pretreated with Pam3CSK4 was decreased significantly compared with that from PBS-treated mice,respectively. Pam3CSK4 pretreatment down-regulated the relative expression of TLR2, inhibited the expression of IRAK-1 and the phosphorylation of NF-κB post infection. The expression of IRAK-M,one of the negative regulators in TLRs signaling pathway was increased significantly in renal tissue from Pam3CSK4-treated mice post infection. Conclusion:Pam3CSK4 pretreatment attenuated the inflammation response in kidney from mice with systemic MRSA infection,and these attenuation is related with up-regulation of IRAK-M.
ABSTRACT
Objective:To study the expression and clinical relevance of IRAK-M in monocytes in patients with systemic lupus erythematosus. Methods: Real-time quantitative PCR was performed for IRAK-M mRNA measurement and enzyme-linked immunosorbent assay was used for anti-double-stranded DNA antibody ( dsDNA ) and anti-single-stranded DNA antibody ( ssDNA ) . Dynamic scattering turbidimetric immunoassay was applied for complement 3(C3),complement 4(C4) and C-reactive protein(CRP), while Westergren method for erythrocyte sedimentation rate (ESR). Correlation analysis of IRAK-M with SLEDAI,dsDNA,ssDNA,C3, C4,CRP and ESR was computed by Pearson or Spearman. Results:①The result showed that the mRNA expression of IRAK-M in SLE patients was significantly lower than healthy controls (P0. 05). Conclusion: This study indicated that IRAK-M play certain significant roles in the pathogenesis of SLE. We can monitor SLE disease activity and prognosis by quantitative detection of mRNA expression of IRAK-M. Meanwhile,it is very necessary to routinely test and regularly monitor the levels of dsDNA,ssDNA,C3,C4,CRP and ESR in SLE.
ABSTRACT
Different environmental and genetic factors have been attributed to the etiology of colorectal cancer. Dysbiotic gut microbiota is associated with initiation and progression of colon carcinogenesis. Hyperactivation of STAT3 promotes carcinogenesis by upregulating cell proliferation, survival, tumor-induced immunosupression and angiogenesis. IRAK-M is a negative regulator of toll-like receptor signaling and inhibits innate immune response. The cancer cell may exploit this property of IRAK-M and evade host immune surveillance. Recently, it has been found that IRAK-M provide controlled feed back to bacteria involved in colorectal cancer by reducing antibacterial response in mice. Furthermore, IRAK-M increased the stability of STAT3 in tumor cells that support tumor promotion by upregulating cell proliferation and survival. Thus, it is suggested that IRAK-M promotes colitis associated colon cancer by enhancing bacterial colonization and stabilization of STAT3.