Sesquiterpene lactones influence IL-6 secretion of keratinocytes and thereby modulate CD54 expression of fibroblasts

Sesquiterpene lactones (STL) are known as the allergy causing principle in Asteraceae species. It is known that low molecular weight haptens, in addition to the capability to form full allergens, must elicit pro-inflammatory signals to trigger an immune reaction in the skin. Keratinocytes are the first cell population that encounters a hapten and are therefore believed to secrete such signals [1]. In an effort to identify the hitherto unknown „danger-signals“ in the case of STL, we found elevated levels of interleukin-6 (IL-6, detected by ELISA) in cell culture supernatants of keratinocytes (HaCaT cell line) treated with STL (helenalin, alantolactone, costunolide, dehydrocostuslactone) or the strong sensitizer dinitrochlorobenzene (DNCB). The STL parthenolide, however, displayed a contrary effect, i.e. a decrease of IL-6 concentration below control level. Subsequently, we investigated the influence of keratinocyte supernatants on the expression of the adhesion molecule CD54 (ICAM-1) on normal human dermal fibroblasts (NHDF). CD54 enables fibroblasts to bind T-Lymphocytes via LFA-1 and should play a role in T-cell mediated skin reactions. Supernatants of HaCaT treated with STL, again with the exception of parthenolide, caused an increase of CD54 expression on NHDF. Consistently, we could show that addition of anti-IL-6-antibodies counteracted the CD54 up-regulation. However, NHDF treated directly with IL-6 did not show a CD54 up-regulation. We conclude that an increase in IL-6 caused by STL is involved in the observed modulation of CD54-expression but not its sole cause. Search for further signalling factors contributing to these effects besides IL-6, including a PIQOR-Microarray, is in progress.

Acknowledgements: Financial support from brial allergen GmbH, Greven, is gratefully acknowledged.

References: 1. Gober, M., Gaspari A. (2008) Curr. Dir. Autoimmun. 10: 1–26.