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.