Rabbit Anti-Human ITGB6 (internal) Polyclonal antibody

Hepatic expression of the transcription factor early growth response-1 (Egr-1) is increased in livers of patients with cholestatic liver disease. Bile acid induction of inflammatory genes in hepatocytes is Egr-1 dependent, and Egr-1 expression is increased in livers of mice after bile duct ligation. Of importance, Egr-1 deficiency reduces liver inflammation and injury in that model. However, it is not known whether Egr-1 promotes inflammation in other models of cholestasis. We tested the hypothesis that Egr-1 contributes to liver inflammation in mice exposed chronically to the bile duct epithelial cell (BDEC) toxicant alpha-naphthylisothiocyanate (ANIT). Egr-1-knockout (Egr-1(-/-)) mice and wild-type mice were fed a diet containing 0.025% ANIT for 2 weeks. Expression of Egr-1 mRNA and protein was significantly increased in livers of mice fed ANIT diet. Egr-1 deficiency did not significantly affect ANIT diet-induced hepatocellular injury, inflammatory gene induction, BDEC hyperplasia, or hepatic neutrophil accumulation. In contrast, the deposition of Type 1 collagen was significantly increased in livers of Egr-1(-/-) mice fed ANIT diet compared with wild-type mice fed ANIT diet. Interestingly, this increase in liver fibrosis occurred in association with elevated expression of the beta 6 integrin (Itgb6) gene, suggesting the potential for increased local activation of transforming growth factor beta. Taken together, the results indicate that Egr-1 does not contribute to liver injury or inflammation in mice fed a diet containing ANIT. Rather, these studies indicate that Egr-1 deficiency worsens liver fibrosis in conjunction with enhanced expression of the profibrogenic Itgb6 gene.

Transforming growth factor beta activation by the alpha v beta 6 integrin is central to the pathogenesis of idiopathic pulmonary fibrosis. Expression of the alpha v beta 6 integrin is increased in fibrotic lung tissue and is a promising therapeutic target for treatment of the disease. Currently, measurement of alpha v beta 6 integrin levels in the lung requires immunohistochemical analysis of biopsy samples. This procedure is clinically impractical for many patients with pulmonary fibrosis, and a noninvasive strategy for measuring alpha v beta 6 integrin levels in the lungs is urgently required to facilitate monitoring of disease progression and therapeutic responses. Methods: Using a murine model of bleomycin-induced lung injury, we assessed the binding of intravenously administered In-111-labeled alpha v beta 6-specific (diethylenetriamine pentaacetate-tetra [DTPA]-A20FMDV2) or control (DTPA-A20FMDVran) peptide by nanoSPECT/CT imaging. Development of fibrosis was assessed by lung hydroxyproline content, and alpha v beta 6 protein and itgb6 messenger RNA were measured in the lungs. Results: Maximal binding of In-111-labeled A20FMDV2 peptide to alpha v beta 6 integrins was detected in the lungs 1 h after intravenous administration. No significant binding was detected in mice injected with control peptide. Integrin binding was increased in the lungs of bleomycin-, compared with saline-, exposed mice and was attenuated by pretreatment with alpha v beta 6-blocking antibodies. Levels of In-111-labeled A20FMDV2 peptide correlated positively with hydroxyproline, alpha v beta 6 protein, and itgb6 messenger RNA levels. Conclusion: We have developed a highly sensitive, quantifiable, and noninvasive technique for measuring alpha v beta 6 integrin levels within the lung. Measurement of alpha v beta 6 integrins by SPECT/CT scanning has the potential for use in stratifying therapy for patients with pulmonary fibrosis.