Cigarette smoke extract suppresses human dendritic cell function leading to preferential induction of Th-2 priming.
J Immunol
; 175(4): 2684-91, 2005 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-16081845
ABSTRACT
Dendritic cells (DC) are key regulators of immune responses. In the current study, we hypothesized that cigarette smoke-induced aberrance in DC function is an important mechanism by which smokers develop cancer, infection, and allergy--diseases common in smokers. We demonstrate that cigarette smoke extract (CSE) inhibits DC-mediated priming of T cells, specifically inhibiting the secretion of IFN-gamma whereas enhancing the production of IL-4 in the MLR. Conditioning with CSE did not effect cytokine (IL-10, IL-6, or IL-12) production from immature DCs, but significantly inhibited IL-12p70 release by LPS-matured DCs. In contrast, IL-10 secretion by LPS-activated CSE-conditioned DCs was enhanced when compared with control DCs. CSE also induced cyclooxygenase-2 protein levels in maturing DCs and significantly augmented endogenous PGE2 release. Conditioning of DCs with CSE also suppressed LPS-mediated induction of CD40, CD80, and CD86, and suppressed maturation-associated CCR7 expression. Although CSE has been reported to induce apoptosis of fibroblasts and epithelial cells, the immunomodulatory effects observed with CSE were not due to diminished DC viability. The effects of CSE on DC function were not exclusively mediated by nicotine, because equivalent, or even higher concentrations of nicotine than those found in CSE, failed to suppress DC-induced T cell priming. These data provide evidence that soluble components extracted from cigarette smoke suppress key DC functions and favor the development of Th-2 immunity.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Humo
/
Células Dendríticas
/
Activación de Linfocitos
/
Células Th2
/
Inmunosupresores
/
Nicotina
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos