This current study and the recent work of Wang et al suggests an oncogenic role for Gremlin in thoracic malignancies. This difference in tumor-suppressive or tumor-proliferative role for Gremlin appears to be a cell-type dependent effect. Topol et al and Chen et al have shown previously that overexpression of Gremlin can inhibit proliferation in tumor-derived cell lines Daoy and Saos-2. This finding is in concordance with published microarray data showing that Gremlin is consistently downregulated in tumors of the CNS in comparison to matched normals. Thus, overexpression of Gremlin in certain organs such as lung may promote tumor growth, while down-regulation of Gremlin in other organs such as brain may inhibit tumor growth. The mechanism by which Gremlin enhances proliferation in lung AD PB 203580 remains unclear. Recent developments in the role of BMP2/4 in tumorigenesis and Gremlin’s role in angiogenesis may provide novel directions to elucidate the mechanism by which Gremlin can induce proliferation in lung AD. The ability of Gremlin to antagonize members of the BMP family has previously been well-documented. However, the role of the BMP2/4 proteins in tumorigenesis is controversial. As recently reviewed by Singh and Morris, the BMP2/4 proteins are commonly shown to have anti-tumorigenic roles, such as the negative regulation of A549 cell line growth by BMP4 in Buckley, et al. However, BMP2 has been shown in some settings to enhance tumor growth in vivo due to activation of Smad-1/5. Gremlin can bind the VEGF receptor-2 in a BMPindependent manner. This binding activates VEGFR2 in endothelial cells, culminating in a VEGFR2-dependent angiogenic response in vitro and in vivo. In addition, Costello et al identified Gremlin as a highly significant member of a 90 gene cohort selectively upregulated in hypoxic primary human pulmonary microvascular cells. We tested whether increased normal lung cell growth induced by GREM1 transfection was BMP2-dependent. MRC-5 fibroblast cells with GREM1 transfection were incubated with BMP2. Addition of high-concentration BMP-2 had no effect on the growth of GREM1-transfected cells. This suggests that GREM1 increases cell growth through a BMPindependent pathway and further study will be required to better elucidate the mechanism for the tissue-specific function of Gremlin. In summary, we present evidence that Gremlin is significantly overexpressed in human adenocarcinoma of the lung. Overexpression of Gremlin increases proliferation of both lung epithelial and fibroblast cell lines. Taken together, these studies suggest an oncogenic role for Gremlin in lung adenocarcinoma. RA, a systemic autoimmune disease, is characterized by chronic joint inflammation, cartilage destruction and bone erosions. Numerous experimental data indicate that IL-17A plays an important role in the pathogenesis of RA. IL-17-deficient mice demonstrate a markedly attenuated form of collagen-induced arthritis, neutralization of IL17 during induction of experimental arthritis suppresses the onset of disease, and anti-IL-17 therapy in established CIA is associated with a significant reduction of severity. IL-17 is implicated in the development of bone erosions by altering the RANKL/OPG balance, and its action may be independent of TNF-a. In human studies, IL-17 is spontaneously produced by RA synovial membrane cultures, high levels have been observed in the synovial fluid of patients with RA, IL-17 producing CD4+ T cells have been detected in RA synovial membranes and neutralization of IL-17 seems to be effective in RA clinical trials.