TY - JOUR
T1 - The role of interleukin-6 in UVA protection against UVB-induced immunosuppression
AU - Reeve, V E
AU - Tyrrell, Rex M
AU - Allanson, M
AU - Domanski, D
AU - Blyth, L
PY - 2009/6
Y1 - 2009/6
N2 - The proinflammatory cytokine IL-6 is released in the skin following UVB irradiation, but its potential for photoimmune modulation remains unclear. This study utilizes IL-6-deficient mice to demonstrate that IL-6 does not contribute to the normal contact hypersensitivity response, nor to its systemic suppression by UVB radiation or cis-urocanic acid. In contrast, IL-6 was required for the attenuation of UVB- or cis-urocanic acid-induced immunosuppression by sequential or concomitant UVA irradiation. The IL-6 was essential for several reactions previously established to be relevant for UVA photoimmune protection, namely the induction of heme oxygenase-1 (HO-1), the activity of its product carbon monoxide in activating guanylyl cyclase, and the consequent elevation of cutaneous cyclic guanosine monophosphate concentration. In addition, IL-6-deficient mouse skin had an elevated constitutive overexpression of HO activity, apparently not associated with photoimmune protection. This suggested that both the cutaneous level of HO activity, and the receptiveness of the HO-1 gene to stressors like UVA, normally controlled by promoter-binding repressor proteins, may also be under IL-6 control. Thus IL-6 has an important photoimmune protective function through interaction at several levels in the pathway determining the immunologically advantageous actions of UVA radiation. This may constitute a valuable endogenous antiphotocarcinogenic regulatory mechanism.
AB - The proinflammatory cytokine IL-6 is released in the skin following UVB irradiation, but its potential for photoimmune modulation remains unclear. This study utilizes IL-6-deficient mice to demonstrate that IL-6 does not contribute to the normal contact hypersensitivity response, nor to its systemic suppression by UVB radiation or cis-urocanic acid. In contrast, IL-6 was required for the attenuation of UVB- or cis-urocanic acid-induced immunosuppression by sequential or concomitant UVA irradiation. The IL-6 was essential for several reactions previously established to be relevant for UVA photoimmune protection, namely the induction of heme oxygenase-1 (HO-1), the activity of its product carbon monoxide in activating guanylyl cyclase, and the consequent elevation of cutaneous cyclic guanosine monophosphate concentration. In addition, IL-6-deficient mouse skin had an elevated constitutive overexpression of HO activity, apparently not associated with photoimmune protection. This suggested that both the cutaneous level of HO activity, and the receptiveness of the HO-1 gene to stressors like UVA, normally controlled by promoter-binding repressor proteins, may also be under IL-6 control. Thus IL-6 has an important photoimmune protective function through interaction at several levels in the pathway determining the immunologically advantageous actions of UVA radiation. This may constitute a valuable endogenous antiphotocarcinogenic regulatory mechanism.
UR - http://www.scopus.com/inward/record.url?scp=67349267808&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1038/jid.2008.377
U2 - 10.1038/jid.2008.377
DO - 10.1038/jid.2008.377
M3 - Article
SN - 0022-202X
VL - 129
SP - 1539
EP - 1546
JO - Journal Of Investigative Dermatology
JF - Journal Of Investigative Dermatology
IS - 6
ER -