TY - JOUR
T1 - Codeine induces human mast cell chemokine and cytokine production
T2 - Involvement of G-protein activation
AU - Sheen, C. H.
AU - Schleimer, R. P.
AU - Kulka, M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/5
Y1 - 2007/5
N2 - Background: Activation of mast cells and the systemic release of histamine are common side effects of opiates such as codeine and morphine. In some individuals, codeine not only elicits a sizable early response due to mast cell degranulation, but can also lead to late cutaneous allergic inflammation possibly through the production of chemokines. However, individuals who exhibit a late phase reaction to codeine often do not react to its synthetic analog, meperidine. The goal of this study was to test whether codeine and meperidine induce secretion of inflammatory mediators in human mast cells. Methods: To characterize opiate activation of human mast cells, we stimulated cultured human (LAD2 cell line and CD34+-derived) mast cells with codeine and meperidine and measured degranulation and chemokine production. Results: Codeine, but not meperidine, activated human mast cell degranulation within 30 min in a dose-dependent manner. Degranulation was blocked by the phosphoinositol-3 kinase (PI3K) inhibitor, wortmannin, and pertussis toxin but not by Ro-31-8220, a PKC inhibitor or forskolin, a cyclic adenylyl cyclase activator. After 3 and 8 h of stimulation, codeine, but not meperidine, activated human mast cells to release monocyte chemoattractant protein-1 (CCL2), regulated on activation, normal T expressed and secreted (RANTES, CCL5) and interleukin-8 (CXCL 8) but not inducible protein-10 (CXCL10). Conclusions: Codeine activates human mast cell degranulation and chemokine production by activating protein kinase A and PI3 kinase, possibly leading to NF-κB activation. Therefore, opiates may regulate late phase allergic inflammation by activating chemokine production by human mast cells.
AB - Background: Activation of mast cells and the systemic release of histamine are common side effects of opiates such as codeine and morphine. In some individuals, codeine not only elicits a sizable early response due to mast cell degranulation, but can also lead to late cutaneous allergic inflammation possibly through the production of chemokines. However, individuals who exhibit a late phase reaction to codeine often do not react to its synthetic analog, meperidine. The goal of this study was to test whether codeine and meperidine induce secretion of inflammatory mediators in human mast cells. Methods: To characterize opiate activation of human mast cells, we stimulated cultured human (LAD2 cell line and CD34+-derived) mast cells with codeine and meperidine and measured degranulation and chemokine production. Results: Codeine, but not meperidine, activated human mast cell degranulation within 30 min in a dose-dependent manner. Degranulation was blocked by the phosphoinositol-3 kinase (PI3K) inhibitor, wortmannin, and pertussis toxin but not by Ro-31-8220, a PKC inhibitor or forskolin, a cyclic adenylyl cyclase activator. After 3 and 8 h of stimulation, codeine, but not meperidine, activated human mast cells to release monocyte chemoattractant protein-1 (CCL2), regulated on activation, normal T expressed and secreted (RANTES, CCL5) and interleukin-8 (CXCL 8) but not inducible protein-10 (CXCL10). Conclusions: Codeine activates human mast cell degranulation and chemokine production by activating protein kinase A and PI3 kinase, possibly leading to NF-κB activation. Therefore, opiates may regulate late phase allergic inflammation by activating chemokine production by human mast cells.
KW - Chemokines
KW - Codeine
KW - Human
KW - Innate immunity
KW - Mast cells
KW - Opiate receptors
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U2 - 10.1111/j.1398-9995.2007.01345.x
DO - 10.1111/j.1398-9995.2007.01345.x
M3 - Article
C2 - 17441793
AN - SCOPUS:34247236607
VL - 62
SP - 532
EP - 538
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
SN - 0105-4538
IS - 5
ER -