LIGHT mediates inflammation in psoriasis by up-regulating cellular proliferation and cytokines production of keratinocytes

Background: The pathogenesis of psoriasis is associated with perturbations of immune system. In our previous studies, HVEM served as a LIGHT (homologous to lymphotoxins, inducible, and competes with HSV glycol- protein D), which is also known as receptors for tumor necrosis factor superfamily member 14. HVEM and LTBR were increased in psoriasis compared with health control, revealing a potential correlation in the pathogenesis of psoriasis. Methods The objective of this study was to examine LIGHT’s effect on keratinocytes proliferation and its therapeutic potential for psoriasis. We added LIGHT protein, anti-HVEM, anti-LTβR, HVEM interference, LTβR interference, NF-κB inhibitor and JNK/AP-1 inhibitor separately or simultaneously in HaCat cells medium in vitro. The expression of NF-κB was stained by immunofluorescence and the expression of inflammatory products was measured with Western blot and ELISA. HaCat cells viability was examined by CCK-8 kit. Flow cytometry was used to detected the expression of HVEM and LTβR on cells and immunohistochemistry in tissues. Results We found that NF-κB transferred from cytoplasm into nuclear after HaCat cells stimulated by LIGHT protein. The expression of p-c-Jun, IL-6, IL-8, PGI2 and PTGS2 was increased when adding LIGHT protein, while decreased after blockading LIGHT’s receptors or inhibiting NF-κB and JNK/AP-1. HaCat cells viability was consistent with the expression of pro-inflammatory factors. The expression of LIGHT and HVEM was increased in lesions of patients with psoriasis. Conclusions These results suggest that JNK/AP-1-HVEM-LIGHT pathway improved the viability and the expression of IL-6, IL-8, PGI2 and PTGS2 in human keratinocytes, revealing the JNK/AP-1-HVEM-LIGHT pathway can be a potential target for the treatment of psoriasis.