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Publication : Activation of gp130 signaling in vivo by the IL-6 super-agonist K-7/D-6 accelerates repopulation of lymphoid organs after irradiation.

First Author  Frasca D Year  1999
Journal  Eur J Immunol Volume  29
Issue  1 Pages  300-10
PubMed ID  9933112 Mgi Jnum  J:52916
Mgi Id  MGI:1330658 Doi  10.1002/(SICI)1521-4141(199901)29:01<300::AID-IMMU300>3.0.CO;2-J
Citation  Frasca D, et al. (1999) Activation of gp130 signaling in vivo by the IL-6 super-agonist K-7/D-6 accelerates repopulation of lymphoid organs after irradiation. Eur J Immunol 29(1):300-10
abstractText  Stimulation of the gp130 signaling pathway by IL-6 is known to contribute significantly to hematopoietic expansion in vitro, mostly in combination with other cytokines. In the present study we have investigated whether a similar effect can be observed also in vivo using shortterm assays in which irradiated mice were analyzed for repopulation of lymphoid organs. Mice were injected with a combination of soluble IL-6R alpha either with wild-type (wt) human IL-6 or with an IL-6 variant, called K-7/D-6, that shows a 70-fold higher IL-6R alpha affinity. We observed that while wt IL-6 was able to induce a partial effect only in combination with IL-3, K-7/ D-6 bypassed the need for IL-3 and yielded complete recovery. In lethally irradiated mice reconstituted with syngeneic bone marrow cells K-7/D-6 strongly accelerated the repopulation of thymus and spleen and hastened blood neutrophil recovery. These results underscore the potential of the gp130 signaling pathway in hematopoietic reconstitution after myeloablative regimens and open the possibility to fully exploit it with a super-active IL-6 variant.
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