Alveolar type II epithelial cells produce interleukin-6 in vitro and in vivo. Regulation by alveolar macrophage secretory products.

Abstract

The aims of this study were (a) to determine if rat alveolar type II (ATIl) cells and human pulmonary epithelial-derived cells (A549 cell line) could generate (b) to characterize the cytokine regulation of IL-6 gene and protein expression in these cells, and (c) to detect the in vivo expression of immunoreactive IL-6 by human ATH cells. Rat ATH cells in primary culture secreted bioactive IL-6 and immunostained with an anti-IL-6 antiserum. Spontaneous IL-6 secretion by rat ATH cells amounted to 5,690±770 pg/ml/106 cells (n = 12) and was fivefold higher than spontaneous rat alveolar macrophages IL-6 secretion (1,052±286 pg/ml/106 cells, n = 8, P = 0.001). Rat alveolar macrophage conditioned media (CM) increased IL-6 secretion by rat ATH cells through the effect of IL-1 and TNF. IL-6 gene expression and IL-6 secretion by A549 cells was induced by 1L-lfi, TNFa, and by human alveolar macrophages and THP1 cells CM. Induction was abolished when CM were preincubated with anti-IL-lfi and anti-TNFa antibody. The combination of IFNy and LPS induced the expression of IL-6 mRNA by A549 cells whereas LPS alone had no effect. Immunohistochemical staining evidenced the expression of immunoreactive 1L-6 by hyperplastic ATHI cells in fibrotic human lung, a condition in which alveolar macrophages are known to be activated. ATII cells in normal human lung did not express immunoreactive 1L-6.Our findings demonstrate that ATH cells may be an important source of 1L-6 in the alveolar space thereby participating to the regulation of the intra-alveolar immune response. (J. Clin. Invest. 1994. 94:731-740.)

Cytoplasmic deposition of NFκB decoy oligonucleotides is insufficient to inhibit bleomycin-induced pulmonary inflammation

“…Firstly, although almost every lung cell and inflammatory cell has been implicated in the pathogenesis of bleomycin-induced pulmonary fibrosis, the relative importance of individual cell types in this process has not been established yet. For example, the proinflammatory cytokine IL-6 can be produced by alveolar and bronchial epithelial cells, 37,38 as well as alveolar macrophages. 39 Smith et al 28 have proposed a cytokine network where initially TNF-␣ and IL-6 are secreted from airway epithelial cells and resident alveolar macrophages, leading to recruitment and stimulation of additional inflammatory cells into the lesion area.…”

Bradykinin Stimulates Type II Alveolar Cells to Release Neutrophil and Monocyte Chemotactic Activity and Inflammatory Cytokines

“…These cells retained many of the characteristics of normal type II cells such as surfactant protein, cytoplasmic multilamellar inclusion bodies, and cuboidal appearance and had been extensively used to assess type II pneumocyte effecter cell functions. 15,21,28 A549 cells were grown as monolayers on 100-mm tissue culture dishes with supplemented F-12 medium as previously reported. 19 The cells from monolayers were harvested with trypsin (0.25%) and EDTA (0.1%) in PBS, centrifuged at low speed (250 ϫ g for 5 minutes), and resuspended in fresh medium at the concentration of 1.0 ϫ 10 6 cells/ml in 35-mm tissue culture dishes.…”

“…18 Moreover, ATII cells are located to have a role in modulating immunological activity in the alveolar space. In this setting, ATII cell line, A549 cells secreted monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)-␤, and leukotriene (LT)B4 constitutively 19 and further secreted interleukin (IL)-8, 15,20 IL-6, 21 interferon, 22 and MCP-1 23 in response to IL-1␤ and tumor necrosis factor (TNF)-␣, suggesting participation in the intra-alveolar cytokine network.…”

Expression and Function of the C5a Receptor in Rat Alveolar Epithelial Cells

“…Although there is evidence that AEC have the ability to produce cytokines and chemokines, most studies with AEC have used the cell line A549, which originally derived from a human bronchoalveolar carcinoma and may not be representative of the features of primary cultures of AEC. In rat AEC (RAEC), the production of five cytokines has been described: TNF-␣, macrophage inflammatory protein-2 (MIP-2), IL-6, monocyte chemoattractant protein-1, and IL-1␤ (1)(2)(3)(4)(5). In addition, AEC also have the ability to generate several complement components (6).…”