IK cytokine ameliorates the progression of lupus nephritis in MRL/lprmice

Abstract

Objective. IK cytokine has been isolated as a factor that inhibits interferon-␥ (IFN␥)-induced expression of class II major histocompatibility complex (MHC) antigens. Aberrant expression of class II MHC antigens has reportedly been recognized in the target organs of autoimmune diseases and been associated with disease activity. In this study, we investigated whether IK cytokine can ameliorate the progression of lupus nephritis in MRL/lpr mice. Methods. A truncated IK analog was prepared and transfected into a nonmetastatic fibroblastoid cell line, and then injected subcutaneously into MRL/lpr mice at ages 8 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease).Results Conclusion. We prepared a potent IK analog and demonstrated its ability to ameliorate the progression of lupus nephritis. This agent may therefore provide a new therapeutic approach for lupus nephritis.

IK Induced by Coxsackievirus B3 Infection Transiently Downregulates Expression of MHC Class II Through Increasing cAMP

“…S2A). These data are consistent with previous studies (33,49). We also identified a reduction in the mRNA levels of other MHC class II accessory molecules, Ii chain and HLA-DM, with the quantitative real-time RT-PCR analysis of tIK-transfected Raji B cells at 24-48 h after transfection ( Supplementary Fig.…”

“…Therefore, we used this cell line as the endogenous-IKgene-negative cells to analyze the role of IK. A previous study showed that truncated IK (tIK), encoded by a 0.72-kb fragment of IK (residues 316-557), is functional in transfected cells (33). Furthermore, the treatment with exogenous tIK protein caused a reduction in IFNc-induced MHC class II expression in murine macrophage cell lines (33).…”

“…A previous study showed that truncated IK (tIK), encoded by a 0.72-kb fragment of IK (residues 316-557), is functional in transfected cells (33). Furthermore, the treatment with exogenous tIK protein caused a reduction in IFNc-induced MHC class II expression in murine macrophage cell lines (33). In this study, to analyze the role of tIK in MHC class II regulation during CVB3 infection, we constructed a plasmid encoding Hemagglutinin (HA)-tagged tIK, designated pcDNA-HAtIK (Fig.…”

“…It has been reported that IK is an efficient inhibitor of IFNc-induced MHC class II expression and it was originally isolated from the conditioned culture medium of the K562 erythroleukemic cell line (25). IK has also been implicated in the inhibition of constitutive MHC class II expression through the repression of class II transactivator (CIITA) (33,49), a factor that regulates MHC class II expression (10,43). However, the detailed cellular mechanism of IK action remains to be clarified.…”

“…However, the detailed cellular mechanism of IK action remains to be clarified. One study showed that the truncated IK (tIK) protein, which includes the 242 amino acids from residue 316 (methionine) to residue 557 (tyrosine), is incapable of localizing in the nucleolus because the 315 amino acid residues are deleted from the N-terminus of the full-length IK protein, but still functions in reducing MHC class II expression (2,33). Therefore, it has been suggested that tIK affects MHC class II expression through its interaction with several unknown cellular factors in the cytoplasm (49).…”