The multifunctional cytokine p43 acts on endothelial and immune cells to control angiogenesis and inflammation. In this report, we describe an additional activity of p43 that specifically promotes fibroblast proliferation and wound repair. In skin wound regions from mice, tumor necrosis factor-␣ induced p43 expression and secretion from macrophages recruited to the site. p43 also promoted fibroblast proliferation through its 146-amino acid N-terminal domain as revealed by deletion mapping. This p43-induced fibroblast proliferation was mediated by extracellular signal-regulated kinase (Erk). Depletion of endogenous p43 in mice by gene disruption retarded wound repair, whereas exogenous supplementation of recombinant human p43 to the wound area stimulated dermal fibroblast proliferation, collagen production, and wound closure. Thus, we have identified a novel p43 activity involving the stimulation of fibroblast proliferation, which could be applied therapeutically to aid wound repair. (Am J Pathol 2005, 166:387-398)

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-γ has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-γ were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Rα1/α2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-γ levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Rα1, rather than IL-13Rα2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.

The peel of Citrus sunki Hort. ex tanaka has been widely used in traditional Asian medicine for the treatment of many diseases, including indigestion and bronchial asthma. In this study, we investigated the antiobesity activity of immature C. sunki peel extract (designated CSE) using high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. In the animal study, body weight gain, adipose tissue weight, serum total cholesterol, and triglyceride in the CSE-administered group decreased significantly compared to the HFD group. Also, CSE supplementation reduced serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and lactate dehydrogenase. Moreover, it significantly decreased the accumulation of fatty droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Dietary supplementation with CSE reversed the HFD-induced decrease in the phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which are related to fatty acid β-oxidation, in the epididymal adipose tissue. Also, CSE increased AMPK and ACC phosphorylation in mature 3T3-L1 adipocytes. CSE also enhanced lipolysis by phosphorylation of cAMP-dependent protein kinase (PKA) and hormone-sensitive lipase (HSL) in mature 3T3-L1 adipocytes. These results suggest that CSE had an antiobesity effect via elevated β-oxidation and lipolysis in adipose tissue.

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