Keratinocytes as effectors in allergic contact dermatitis towards sesquiterpene lactones – Different behavior of HaCaT and NHEK cells

In allergic contact dermatitis (ACD) keratinocytes (KC) contribute to the sensitization phase as well as the elicitation of the skin reaction after hapten contact. One of the best known mechanisms of this pathological reaction is the release of pro-inflammatory mediators by these skin cells. After hapten contact such mediators are able to enhance the immunological reaction, which can lead to an impaired regulation of the immune reaction and result in a contact allergic reaction [1].

Among the many natural compounds causing ACD, sesquiterpene lactones (STL) from Asteraceae are well known. To investigate the contribution of KC to the onset of STL-related ACD by production of proinflammatory mediators, supernatants of KC cultures treated with STL were examined by ELISA for the concentration of TNF-α, IL-6, IL-8 and IFN-γ. In case of HaCaT-KC a strong increase of IL-6 as well as IL-8 was observed for most of the tested STL as well as the positive control dinitrochlorobenzene (DNCB) [2]. Most interestingly this effect could not be observed with normal human epidermal keratinocytes (NHEK) treated with STL or DNCB.

Quite interestingly, however, supernatants of both HaCaT as well as NHEK increased the expression of intercellular adhesion molecule 1 (ICAM-1 or CD54) on normal human dermal fibroblasts (NHDF). This effect was enhanced by the test compounds in HaCaT but diminished in NHEK cultures.

These findings implicate a possible involvement of KC in the ACD towards STL by means of altered secretion of proinflammatory mediators. Yet the differing results in the two cell model systems are quite interesting. Further studies will have to investigate the detailed reason for this discrepancy and address the question, whether either of those models is more reliable than the other in studies on inflammatory/immunological processes.

References:

[1] Albanesi C., Curr. Opin. Allergy Clin. Immunol., 10, 452 – 456, 2010

[2] Hoffmann MKF, Schmidt TJ, Planta Med. 78, 1138, 2012