[Induction of tumor cell killing by human alveolar macrophages and its regulation by IL-4].
The present study was undertaken to examine the effects of IL-4 on induction of cytotoxic killer activity and on production of antitumor mediators by human monocytes and alveolar macrophages (AM). The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4. Addition of IL-4 to cultures of AM or monocytes with endotoxin resulted in dose-dependent suppression of their cytotoxic activity against A375 and its variant cells resistant to IL-1 and TNF-alpha. IL-4 inhibited the production of IL-1 and TNF-alpha by AM at the protein and mRNA levels. Oxygen radical production was also suppressed by treating AM with IL-4. IL-1 receptor antagonist (IL-1ra) was also produced by monocytes stimulated with LPS, but not with IL-4. Marked up-regulation by IL-4 of IL-1ra production in LPS-stimulated monocytes was observed at both the mRNA and protein levels. These findings suggest that IL-4 may be important in down-regulation of antitumor activation of human monocyte-macrophages, not only directly through inhibition of production of antitumor effector molecules, but also indirectly through up-regulation of production of IL-1ra.
Sone
S
S
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
Nishioka
Y
Y
Nii
A
A
Yanagawa
H
H
Orino
E
E
Mizuno
K
K
Yano
S
S
Ogura
T
T
D002478:Cells, Cultured; D015536:Down-Regulation; D005609:Free Radicals; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000502:physiology*; D008545:Melanoma / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D005609:Free Radicals; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017382:Reactive Oxygen Species; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4