Biological activity of limitin and adiponectin

(1)脂联素：脂联素是脂肪细胞的主要产物之一，在长期培养的骨髓细胞中，脂联素强烈抑制B淋巴细胞的生成，但仅在基质细胞存在的情况下。在含有脂联素的基质细胞培养中，COX-2抑制剂取消了早期淋巴祖细胞对脂联素的反应。此外，COX-2活性的主要产物前列腺素E_2对纯化的造血细胞有直接的抑制作用，提示脂联素在培养中可能的作用机制。(2)利米丁：利米丁是一种干扰素样细胞因子，可增强细胞毒性T淋巴细胞的杀伤活性和MHC I类分子的表面表达。利米丁抑制稳定表达p210bcr/ABL的FDCP-1细胞的增殖。利米丁还能诱导抗EMCV、MHV和HSV的抗病毒状态。虽然利米丁的上述功能与干扰素-α相似，但抑制CFU-IL-7或CFU-MEG的集落形成需要比干扰素-α更高的浓度。利米丁不能抑制CFU-GM或BFU-E的集落形成，而干扰素-α则有抑制作用。这些数据表明，利米丁的毒性可能比其他IFN低，因此在治疗I型IFN被证明有效的疾病方面可能有独特的临床利基。在干扰素介导的骨髓抑制信号中，TYK2的阻断完全阻断了干扰素-α对CFU-IL7和CFU-MEG集落形成的抑制作用。我们正在分析Limitin和干扰素-α中TYK2下游信号的差异。免疫组织化学分析表明，Limitin蛋白是由脾和胸腺中成熟的T淋巴细胞结构性产生的。与其他IFN不同，Limitin的表达不会因病毒感染而上调。这些数据可能表明，Limitin的作用是避免病毒感染或在健康条件下消除有害细胞。

(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.