title: Suppressor of cytokine signaling 1 inhibits pulmonary inflammation and fibrosis.
abstract: BACKGROUND
  Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling. Our previous study suggested that SOCS1 regulates collagen synthesis by lung fibroblasts, suggesting a role of SOCS1 in the pathophysiology of pulmonary fibrosis.
  
  
  OBJECTIVE
  We sought to investigate the role of SOCS1 in pulmonary inflammation and fibrosis in vivo.
  
  
  METHODS
  SOCS1-haplodeficient mice treated with bleomycin (BLM) were evaluated for pulmonary inflammation and fibrosis compared with wild-type mice. The human study group was composed of 18 patients with interstitial lung disease. Lung specimens obtained by means of open lung biopsy were investigated to determine whether the severity of fibrosis was associated with decreased SOCS1 expression. Finally, we further analyzed the effect of exogenous SOCS1 on BLM-induced lung injury based on adenoviral SOCS1 gene transfer to the lung.
  
  
  RESULTS
  SOCS1-haplodeficient mice treated with BLM showed markedly enhanced pulmonary inflammation and fibrosis compared with wild-type mice. Using human lung specimens, we found that SOCS1 mRNA levels inversely correlated with duration of the disease. SOCS1 expression was significantly less in lung tissue from patients with idiopathic pulmonary fibrosis (IPF) compared with that in non-IPF patients. Moreover, SOCS1 expression was significantly less in severe fibrotic lesions (lower lobe) than in less fibrotic lesions (upper lobe). Adenoviral SOCS1 gene transfer to murine lungs significantly decreased lymphocytic inflammation, pulmonary fibrosis, and mortality because of BLM-induced lung injury. Exogenous SOCS1 inhibited expression of various cytokines, including TNF-alpha, which might play a key role.
  
  
  CONCLUSIONS
  These results suggest that SOCS1 might act as a suppressor for pulmonary fibrosis. SOCS1 might be a target of IPF treatment.
authors: Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors: Taku
authors: T
authors: Nakashima
authors: Akihito
authors: A
authors: Yokoyama
authors: Yojiro
authors: Y
authors: Onari
authors: Hiroyasu
authors: H
authors: Shoda
authors: Yoshinori
authors: Y
authors: Haruta
authors: Noboru
authors: N
authors: Hattori
authors: Tetsuji
authors: T
authors: Naka
authors: Nobuoki
authors: N
authors: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008875:Middle Aged; D011014:Pneumonia / Q000378:metabolism* / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D001761:Bleomycin