title: Impaired ultraviolet-B-induced cytokine induction in xeroderma pigmentosum fibroblasts.
abstract: Xeroderma pigmentosum is a rare, autosomal recessive disease in which patients develop excessive solar damage at an early age and have a 1000-fold increased risk of developing cutaneous neoplasms. Xeroderma pigmentosum can be classified into seven complementation groups (A-G) with defects in different DNA nucleotide excision repair genes. Xeroderma pigmentosum patients also have impaired immune function including reduced natural killer cell activity and impaired induction of interferon-gamma. We hypothesized that altered cytokine induction may contribute to the immune defect in xeroderma pigmentosum patients. We examined cytokine mRNA expression after ultraviolet B irradiation using reverse transcriptase polymerase chain reaction in fibroblasts derived from five xeroderma pigmentosum patients in complementation groups A, C, and D and in complemented XP-A and XP-D cells. Cytokines interleukin-1beta and interleukin-6 displayed impaired ultraviolet B induction whereas interleukin-8 had normal induction in the xeroderma pigmentosum fibroblasts. Stable complementation of XP-A and XP-D cell lines increased ultraviolet-B-induced interleukin-1beta and interleukin-6 expression. These results demonstrate a deficient response of xeroderma pigmentosum fibroblasts to ultraviolet B in terms of cytokine interleukin-1beta and interleukin-6 induction but normal interleukin-8 induction and exhibit a role for DNA repair in cytokine induction.
authors.affiliation: Division of Dermatology, University of Toronto, Sunnybrook and Women's College Health Science Center, Toronto, Ontario, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: W
authors.initials: W
authors.lastname: Kalair
authors.forename: G M
authors.initials: GM
authors.lastname: Shivji
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Toto
authors.forename: P
authors.initials: P
authors.lastname: Amerio
authors.forename: K H
authors.initials: KH
authors.lastname: Kraemer
authors.forename: D N
authors.initials: DN
authors.lastname: Sauder
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D012016:Reference Values; D014466:Ultraviolet Rays; D015854:Up-Regulation; D014983:Xeroderma Pigmentosum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8