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

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.

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.

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.

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.