Connexin 26 in psoriatic skin before and after two conventional therapeutic modalities: methotrexate and PUVA

Background: Direct intercellular signaling, which controls keratinocyte behavior, proliferation and differentiation, occurs through gap junctions. Altered expression of connexins may play a role in the development of psoriatic lesions. Objectives: We estimated connexin 26 (Cx26) mRNA in psoriatic patients and investigated whether the standard therapeutic modalities (methotrexate and PUVA) exert their anti-psoriatic activity partially through altering Cx26 mRNA levels. We also detected Cx26 in skin biopsies by immunohistochemistry. RT-PCR measured Cx26 mRNA levels in 24 chronic plaque psoriasis patients. Group A received intramuscular methotrexate and group B was treated by PUVA for ten weeks, each followed by measurement of Cx26 mRNA levels and immunohistochemistry. Twelve healthy volunteers served as controls. Results: Cx26 mRNA expression was significantly higher in the patients before treatment than in controls (P < 0.001). Post treatment levels were significantly lower than pre-treatment levels (P < 0.001), however, significantly higher than in controls (P < 0.001). Methotrexate and PUVA caused significant reductions in Cx26 mRNA expression (P = 0.002, P = 0.028 respectively). Post treatment levels were slightly significantly lower in the methotrexate group than in the PUVA group (P = 0.046). The reduction in Cx26 mRNA expression was significantly positively correlated with the clinical improvement of the psoriatic plaque (P = 0.002). Immunostaining of Cx26 decreased after treatment. Conclusion: Altered expression of the gap junction protein Cx26 may have a role in the development of the psoriatic phenotype. Both methotrexate and PUVA significantly lowered the expression of Cx26 mRNA and protein.