Perfluorooctanoic acid induces mast cell-mediated allergic inflammation by the release of histamine and inflammatory mediators.
Perfluorooctanoic acid (PFOA) has unique physical and chemical characteristics, water and oil repellency, thermal stability, and surfactant properties. PFOA has been regularly found in the blood of animals and humans worldwide, and has become an increasing concern because of its adverse effects in immune system. However, the role of PFOA in the allergic inflammation is not well-known. To further extend the immunotoxicity of PFOA, we examined the role of PFOA on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. PFOA dose- and time-dependently increased histamine release from mast cells and serum histamine by the induction of intracellular calcium. PFOA exacerbated the IgE-dependent local allergic reaction in the mouse allergy model. PFOA induced gene expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in mast cells. The inducing effect of PFOA on the pro-inflammatory cytokines was nuclear factor-κB, p38 mitogen-activated protein kinase, and caspase-1 dependent. Furthermore, the activation of cyclooxygenase-2 by PFOA suggests the induction of allergic inflammatory mediators by the PFOA. Our findings provide evidence that PFOA, the known immunotoxic agent, induces mast cell-derived allergic inflammatory reactions by histamine release and expression of pro-inflammatory cytokines.
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Thoudam S K
TS
Singh
Soyoung
S
Lee
Hui-Hun
HH
Kim
Jin Kyeong
JK
Choi
Sang-Hyun
SH
Kim
D000818:Animals; D002118:Calcium / Q000032:analysis; D002210:Caprylates / Q000633:toxicity*; D020170:Caspase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D006636:Histamine Release / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced*; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002210:Caprylates; D005466:Fluorocarbons; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C023036:perfluorooctanoic acid; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D020170:Caspase 1; D002118:Calcium