title: A549 cells can express interleukin-16 and stimulate eosinophil chemotaxis.
abstract: Alveolar epithelial cells produce many types of chemokines such as regulated on activation, normal T cells expressed and secreted (RANTES), eotaxin induced by interleukin (IL)-1 beta, or tumor necrosis factor (TNF)-alpha and may contribute to allergic disease by recruiting eosinophils. However, identification of the eosinophil chemotacic activity (ECA) release from A549 cells, an alveolar type II cell line, has not yet been completed. Recently, IL-16 was also reported to be a potent chemotactic stimulus for CD4(+) T lymphocytes and eosinophils in asthma and other pulmonary diseases. To test the possibility that alveolar epithelial cells produce IL-16, we analyzed RNA and culture supernatant from A549 cells by reverse transcription/ polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The release of ECA from A549 cells was assessed using a blind-well chemotactic chamber. IL-16 release was increased in a concentration-dependent manner by stimulation with IL-1 beta or TNF-alpha. A549 cells also expressed IL-16 messenger RNA. The combination of IL-4 and IL-1 beta or TNF-alpha had an additive effect on IL-16 production. The release of ECA was induced by IL-1 beta or TNF-alpha in a dose-dependent manner. The combination of these cytokines had a greater effect than one alone. The blockade of eotaxin and IL-16 caused 70% inhibition of ECA, but anti-RANTES antibodies only caused 30% inhibition and anti-IL-8 antibodies failed to affect inhibition. These findings suggest a role for chemokines released by alveolar epithelial cells in the recruitment of eosinophils into the lung in pulmonary disorders such as asthma and interstitial lung diseases, and suggested that eotaxin and IL-16 are potent and effective eosinophil chemoattractants.
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan. cheng@dokkyomed.ac.jp
authors.forename: G
authors.initials: G
authors.lastname: Cheng
authors.forename: T
authors.initials: T
authors.lastname: Ueda
authors.forename: F
authors.initials: F
authors.lastname: Eda
authors.forename: M
authors.initials: M
authors.lastname: Arima
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004804:Eosinophils / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D019410:Interleukin-16 / Q000096:biosynthesis* / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D017931:DNA Primers; D007375:Interleukin-1; D019410:Interleukin-16; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4