Expression of orphan receptor GPR15/BOB up-regulated in systemic lupus erythematous/crosstalk with pro-inflammatory cytokines

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that has protean manifestations and follows a relapsing and remitting course. More than 90% of cases of SLE occur in women, frequently starting at childbearing age. The pattern of tissue injury in SLE is primarily related to the formation of the immune complexes deposits that can induce the inflammatory response by activation of adhesion molecules on endothelium, resulting in the recruitment of pro inflammatory leukocytes. The goal of this study was to investigate the expression of orphan receptor GPR15/BOB in the lesion/ peripheral blood of SLE patients and non-SLE patients. Messenger RNA expression was examined by reverse-transcription polymerase chain reaction (RT-PCR) and GPR15/BOB protein by immunofluorescence. Cytokines were analyzed from blood serum using enzyme linked immunoassay (ELISA) for IL-6 and INF-α. Further; GPR15/BOB expression on peripheral blood leukocytes was analysed by flow cytometry. GPR15/BOB (P=0.002) expression levels were significantly increased in lupus patients compared to age-matched controls. African American women with lupus had a 2-fold increase in GPR15/BOB expression level when compared to their healthy controls or European American lupus patients. Serum levels revealed significant increases in expression of IL-6, IFN-γ and TNF-α in lupus patients with expression of GPR15/BOB compared to non-expression of GPR15/BOB -lupus patients. This study shows expression of GPR15/BOB is up-regulation in SLE patients and provides an opportunity for targeting with antagonist as a novel therapy for SLE.