Inhibitor effect of Janus kinase II in bleomycin-induced pulmonary fibrosis model

INTRODUCTION Idiopathic pulmonary fibrosis (IPF) is the interstitial pulmonary disease with higher incidence and worse prognosis. Recent evidence suggests that cucurbitaceae are selective inhibitors of the JAK2/STAT3 pathway. Since P-STAT3 is increased in fibrotic foci of IPF patients, we hypothesis that it may inhibit the progression of the disease. OBJECTIVE The purpose of this study was to evaluate the effect of Cucurbitacin I (CuI) in a murine model of bleomycin-induced pulmonary fibrosis. MATERIAL Y METHODS Wistar rats were instilled intratracheally with a single dose of bleomycin (BLM)(3.75 U/kg; n=12) to induce lung fibrosis. CuI (20mg/kg/day; n=6) or CuI vehicle (control and IPF group) was administered intraperitoneally daily for 21 days. Animal evolution was controlled through CT/SPECT imaging. Tgf-β1, Col1A and Et-1 gene and protein expression was measured by real time PCR and western blott as fibrotic markers. RESULTS CT/SPECT quantification showed reduction of the fibrotic areas in the CuI treated group by reestablishing the air space in the lungs by inhibiting the IPF progression. Tgf-β1, Col1A and Et-1 gene expression was upregulated 2.3, 7.2 and 1.9 fold respectively in BLM relative to Control rats. This was counteracted with CuI treatment. These results were substantiated by protein over-expression of Tgf-β1 (62.30%), Col1A (45.80%) and Et-1 (44.44%) in BLM rat. Protein expression was inhibited in CuI treated group by 32.04%, 30.52% and 44.99% respectively. CONCLUSION CuI inhibits the rat model BLM induced pulmonary fibrosis.