Biological activity of limitin and adiponectin

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(1) Adiponectin: Adiponectin, one of the major products of adipocytes, strongly inhibited B lymphopoiesis in long-term bane marrow cultures, but only when stromal cells were present. Cox-2 inhibitors abrogated the response of early lymphoid progenitors to adiponectin in stromal cell containing cultures. Furthermore, prostaglandin E2, a major product of Cox-2 activity; had a direct inhibitory influence on purified hematopoietic cells, suggesting a possible mechanism of adiponectin action in culture.(2) Limitin: Limitin, an IFN-like cytokine, augmented the killer activity of cytotoxic T lymphocytes as well as the surface expression of MHC class I molecules. Limitin inhibited the proliferation of FDCP-1 cells stably transfected with p210bcr/abl. Limitin also induced antiviral state against EMCV, MHV, and HSV. Although the above functions of limitin were similar to those of IFN-α, higher concentration of limitin was required than IFN-α for the inhibition of CFU-IL7 or CFU-Meg colony formation. Limitin could not inhibit CFU-GM or BFU-E colony formation while IFN-α did. These data suggest that limitin may be less toxic than other IFNs, and therefore may have a unique clinical niche for treatment of diseases where type I IFNs have proven useful. In signals for IFN-mediated myelosuppression, the disruption of Tyk2 completely abrogated IFN-α-induced inhibition of CFU-IL7 and CFU-Meg colony formation. We are now analyzing the difference of downstream signals of Tyk2 between limitin and IFN-α.Immunohistochemical analysis revealed that the limitin protein is constitutively produced by mature T lymphocytes in spleen and thymus. Unlikely other IFNs, limitin expression was not up-regulated by virus-infection. These data may suggest that limitin acts to avoid virus-infection or to eliminate harmful cells in healthy conditions.