IADR Abstract Archives

Novel IL-1 Family Cytokines Stimulate IL-6 Production in Human Keratinocytes

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.


Pan European Federation Meeting
2006 Pan European Federation Meeting (Dublin, Ireland)
Dublin, Ireland
2006
188
Scientific Groups
  • Lea, S. R.  ( University of Newcastle upon Tyne, Newcastle upon Tyne, N/A, United Kingdom )
  • Cui, Yifen  ( University of Newcastle upon Tyne, United Kingdom, , N/A, )
  • Sims, John  ( Amgen, , N/A, )
  • Preshaw, P.m.  ( University of Newcastle upon Tyne, Newcastle upon Tyne, N/A, United Kingdom )
  • Taylor, J. J.  ( University of Newcastle upon Tyne, Newcastle upon Tyne, N/A, United Kingdom )
  • Foster, Neil  ( University of Newcastle upon Tyne, Newcastle upon Tyne, N/A, United Kingdom )
    • Oral Session
    BSDR Junior Colgate Award, BSDR Senior Colgate Award
    09/14/2006