| 0188 Novel IL-1 Family Cytokines Stimulate IL-6 Production in Human Keratinocytes | ||
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S.R. LEA1, Y. CUI1, J. SIMS2, P.M. PRESHAW1, J.J. TAYLOR1, and N. FOSTER1, 1University of Newcastle upon Tyne, United Kingdom, 2Amgen Objectives: Although IL-1 cytokines have an established role in the pathogenesis of inflammatory disorders such as periodontal disease, few reported studies have investigated the biological effect of novel IL-1 family members (IL-1F5-IL-1F10). The aims of the study we report were (1) to determine whether IL-1F6, F8 or IL-F9 had any effect on secretion of IL-6 by a human keratinocyte cell line (HaCaT cells) which is known to produce IL-6 in response to IL-1 β(IL-1F2), (2) to determine whether IL-1F5 (a putative antagonist of IL-1F9) had any effect on these responses and (3) to investigate whether or not novel IL-1 cytokines act through the receptor IL-1Rrp2. Methods: IL-6 production by HaCaT cells was assayed by ELISA. The expression of IL-1Rrp2 protein was determined by confocal microscopy and FACS using specific antibodies. The expression of IL-1Rrp2 mRNA was detected by RT-PCR. Stimulation of HaCaT cells via IL-1Rrp2 was inhibited by blocking antibodies to the receptor. Results: Our data indicate that after 6h stimulation with 50 ng/ml IL-1 family cytokines, only IL-1F2 significantly increased (P <0.05) IL-6 production by HaCaT cells above unstimulated controls. However, after 24h, IL-1F2 and IL-1F8 significantly increased (P<0.05) IL-6 production by HaCaT cells. IL-1F6 and 9 also elevated IL-6 production by HaCaT cells although this did not reach statistical significance. Our preliminary experiments also indicate that IL-1F5 (used at concentrations between 1-80 ng/ml) had no significant effect (P>0.05) on IL-6 production by HaCaT cells stimulated with IL-1F2, F6, F8 or F9. We have also shown that IL-1Rrp2 is expressed by HaCat cells and antibody blocking experiments reveal that novel IL-1 cytokines stimulate IL-6 production in HaCaT cells by acting through IL-1Rrp2. Conclusion: We conclude that novel IL-1 cytokines stimulate HaCaT cells to produce IL-6 via IL-1Rrp2 and that IL-1F5 does not antagonise this effect.
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| Seq #19 - BSDR Junior Colgate Award, BSDR Senior Colgate Award 8:30 AM-10:30 AM, Thursday, 14 September 2006 Trinity College Dublin Walton | ||
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