Abstract:
:Pro-inflammatory cytokines are important mediators of cutaneous cellular activities during many skin diseases. In the present study, we investigated the production of tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-10 by UVB-irradiated human keratinocytes NCTC 2544 cell line in the presence of cAMP-elevating agents and we attempted to determine the implication of cyclic AMP/PKA pathway in the regulation of cytokine gene expression. Cytokine mRNA expression levels and cytokine concentrations were investigated by reverse transcription polymerase chain reaction and by ELISA method, respectively. Treatment of UVB-irradiated NCTC 2544 cells with drugs known to enhance cAMP concentration [dibutyryl cAMP, PGE(2) and cholera toxin] results in a significant decrease of TNF-alpha mRNA expression whereas IL-6 and IL-10 mRNAs were enhanced. In the same experimental conditions, treatment of irradiated keratinocytes with PKA inhibitors [H89 and PKA inhibitor (PKAi)] induced a significant inhibition of mRNA expression for all tested cytokines. Except for IL-10, the pharmacological effect of cAMP-elevating agents or PKA inhibitors on radiation-induced TNF-alpha and IL-6 mRNA expression was associated with a concomitant regulation of cytokine release. Taken together our results showed: (i) a differential regulation of TNF-alpha, IL-6 and IL-10 in UVB-irradiated human keratinocytes via cyclic AMP/protein kinase A pathway, and (ii) a possible reduction of deleterious inflammatory effects of cytokine following UVB-irradiation by using pharmacological agents that regulate both the intracellular cAMP levels and the cellular PKA activity.
journal_name
Cytokinejournal_title
Cytokineauthors
Grandjean-Laquerriere A,Le Naour R,Gangloff SC,Guenounou Mdoi
10.1016/s1043-4666(03)00224-2keywords:
subject
Has Abstractpub_date
2003-08-21 00:00:00pages
138-49issue
4-5eissn
1043-4666issn
1096-0023pii
S1043466603002242journal_volume
23pub_type
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