title: A20 regulates IL-1-induced tolerant production of CXC chemokines in human mesangial cells via inhibition of MAPK signaling.
abstract: Chemokines and chemokine receptors are involved in the resolution or progression of renal diseases. Locally secreted chemokines mediated leukocyte recruitment during the initiation and amplification phase of renal inflammation. However, the regulation of chemokine induction is not fully understood. In this study, we found that IL-1 induced a significant up-regulation of CXC chemokines CXCL1, 2, and 8 at both mRNA and protein levels in human mesangial cells. The induction of chemokines was tolerant, as the pre-treatment of HMC with IL-1 down-regulated the induction of chemokines induced by IL-1 re-stimulation. IL-1 up-regulated the ubiquintin-editing enzyme A20. A20 over-expression down-regulated IL-1-induced up-regulation of chemokines, and A20 down-regulation reversed chemokine inhibition induced by IL-1 pre-treatment, suggested that A20 played important roles in the tolerant production of chemokines. Unexpectedly, A20 over- expression inhibited the activation of ERK, JNK, and P38, but did not inhibit the activation of NF-κB. In addition, both IL-1 treatment and A20 over-expression induced the degradation of IRAK1, an important adaptor for IL-1R1 signaling, and A20 inhibition by RNA interference partly reversed the degradation of IRAK1. Taken together, IL-1-induced A20 negatively regulated chemokine production, suggesting that A20 may be an important target for the prevention and control of kidney inflammation.
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, 410004, China.|Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Urology, Changsha Central Hospital, Changsha, 410004, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Changsha Central Hospital, Changsha, 410004, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, 410004, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Laboratory Medicine, XinXiang Medical University, XinXiang, 453003, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Sun
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, 410004, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Liu
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, 410004, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Medical Research Center, Changsha Central Hospital, Changsha, 410004, China.
authors.forename: Jinyue
authors.initials: J
authors.lastname: Hu
mesh_terms: D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D050527:Mesangial Cells / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism; D053574:Receptors, Interleukin-1 Type II / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3