Abstract
We have evaluated the capacity of cultured human respiratory epithelial cells (HTE) to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) and have examined the ability of proinflammatory stimuli and of glucocorticoids to modulate the production of GM-CSF by these cells. Conditioned medium (CM) was obtained after 24-hr culture of HTE in the presence or absence of serum (5%) and was assayed for GM-CSF activity using the M-07e cell line, which proliferates in response to GM-CSF and interleukin-3 (IL-3). HTE produced 1.1 +/- 0.7 and 2.1 +/- 1.5 ng GM-CSF/10(6) cells in the presence or absence of serum, respectively (n = 4). The identity of this activity as GM-CSF was established by neutralization with specific antibody to GM-CSF, while antibody to IL-3 was without effect. Dexamethasone (10(-6) M) inhibited basal GM-CSF release to below the limit of detection of the assay (0.12 ng GM-CSF/ml conditioned media). GM-CSF release was significantly enhanced by 10(-6) M histamine (1.6 +/- 0.7 versus 2.13 +/- 0.8 ng GM-CSF/10(6) cells; n = 9) and 5 ng/ml interleukin-1 (IL-1) (0.6 +/- 0.2 versus 3.2 +/- 0.5 ng GM-CSF/10(6) cells; n = 3). Stimulation of GM-CSF release by IL-1 was dose-dependent. A significant increase in GM-CSF activity was observed with 0.1 ng/ml, while maximal stimulation occurred at 5 ng/ml IL-1. In kinetic studies, GM-CSF activity was first detected in CM from cells incubated in the absence of stimulus at 8 hr of incubation, and continued to increase up to 24 hr. IL-1 stimulated GM-CSF activity was detected in CM as early as 4 hr and continued to increase significantly up to 24 hr. Thus, human tracheal epithelial cells release GM-CSF and this release is regulated by inflammatory mediators and glucocorticoids.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Avanzi G. C., Brizzi M. F., Giannotti J., Ciarletta A., Yang Y. C., Pegoraro L., Clark S. C. M-07e human leukemic factor-dependent cell line provides a rapid and sensitive bioassay for the human cytokines GM-CSF and IL-3. J Cell Physiol. 1990 Dec;145(3):458–464. doi: 10.1002/jcp.1041450310. [DOI] [PubMed] [Google Scholar]
- Bochner B. S., Charlesworth E. N., Lichtenstein L. M., Derse C. P., Gillis S., Dinarello C. A., Schleimer R. P. Interleukin-1 is released at sites of human cutaneous allergic reactions. J Allergy Clin Immunol. 1990 Dec;86(6 Pt 1):830–839. doi: 10.1016/s0091-6749(05)80143-5. [DOI] [PubMed] [Google Scholar]
- Broudy V. C., Kaushansky K., Harlan J. M., Adamson J. W. Interleukin 1 stimulates human endothelial cells to produce granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor. J Immunol. 1987 Jul 15;139(2):464–468. [PubMed] [Google Scholar]
- Chen B. D., Mueller M., Chou T. H. Role of granulocyte/macrophage colony-stimulating factor in the regulation of murine alveolar macrophage proliferation and differentiation. J Immunol. 1988 Jul 1;141(1):139–144. [PubMed] [Google Scholar]
- Chodakewitz J. A., Kupper T. S., Coleman D. L. Keratinocyte-derived granulocyte/macrophage colony-stimulating factor induces DNA synthesis by peritoneal macrophages. J Immunol. 1988 Feb 1;140(3):832–836. [PubMed] [Google Scholar]
- Churchill L., Chilton F. H., Proud D. Interaction of platelet-activating factor with cultured guinea pig tracheal epithelial cells. Biochem J. 1991 Jun 15;276(Pt 3):593–598. doi: 10.1042/bj2760593. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Churchill L., Chilton F. H., Resau J. H., Bascom R., Hubbard W. C., Proud D. Cyclooxygenase metabolism of endogenous arachidonic acid by cultured human tracheal epithelial cells. Am Rev Respir Dis. 1989 Aug;140(2):449–459. doi: 10.1164/ajrccm/140.2.449. [DOI] [PubMed] [Google Scholar]
- Geissler K., Harrington M., Srivastava C., Leemhuis T., Tricot G., Broxmeyer H. E. Effects of recombinant human colony stimulating factors (CSF) (granulocyte-macrophage CSF, granulocyte CSF, and CSF-1) on human monocyte/macrophage differentiation. J Immunol. 1989 Jul 1;143(1):140–146. [PubMed] [Google Scholar]
- Hancock W. W., Pleau M. E., Kobzik L. Recombinant granulocyte-macrophage colony-stimulating factor down-regulates expression of IL-2 receptor on human mononuclear phagocytes by induction of prostaglandin E. J Immunol. 1988 May 1;140(9):3021–3025. [PubMed] [Google Scholar]
- Hart P. H., Whitty G. A., Piccoli D. S., Hamilton J. A. Synergistic activation of human monocytes by granulocyte-macrophage colony-stimulating factor and IFN-gamma. Increased TNF-alpha but not IL-1 activity. J Immunol. 1988 Sep 1;141(5):1516–1521. [PubMed] [Google Scholar]
- Heidenreich S., Gong J. H., Schmidt A., Nain M., Gemsa D. Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2. J Immunol. 1989 Aug 15;143(4):1198–1205. [PubMed] [Google Scholar]
- Hunninghake G. W. Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis. Am Rev Respir Dis. 1984 Apr;129(4):569–572. [PubMed] [Google Scholar]
- Hunter J. A., Finkbeiner W. E., Nadel J. A., Goetzl E. J., Holtzman M. J. Predominant generation of 15-lipoxygenase metabolites of arachidonic acid by epithelial cells from human trachea. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4633–4637. doi: 10.1073/pnas.82.14.4633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laitinen L. A., Laitinen A., Heino M., Haahtela T. Eosinophilic airway inflammation during exacerbation of asthma and its treatment with inhaled corticosteroid. Am Rev Respir Dis. 1991 Feb;143(2):423–427. doi: 10.1164/ajrccm/143.2.423. [DOI] [PubMed] [Google Scholar]
- Lin H. S., Lokeshwar B. L., Hsu S. Both granulocyte-macrophage CSF and macrophage CSF control the proliferation and survival of the same subset of alveolar macrophages. J Immunol. 1989 Jan 15;142(2):515–519. [PubMed] [Google Scholar]
- Lindemann A., Riedel D., Oster W., Ziegler-Heitbrock H. W., Mertelsmann R., Herrmann F. Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes. J Clin Invest. 1989 Apr;83(4):1308–1312. doi: 10.1172/JCI114016. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- Liu M. C., Bleecker E. R., Lichtenstein L. M., Kagey-Sobotka A., Niv Y., McLemore T. L., Permutt S., Proud D., Hubbard W. C. Evidence for elevated levels of histamine, prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects with mild asthma. Am Rev Respir Dis. 1990 Jul;142(1):126–132. doi: 10.1164/ajrccm/142.1.126. [DOI] [PubMed] [Google Scholar]
- Lopez A. F., Williamson D. J., Gamble J. R., Begley C. G., Harlan J. M., Klebanoff S. J., Waltersdorph A., Wong G., Clark S. C., Vadas M. A. Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival. J Clin Invest. 1986 Nov;78(5):1220–1228. doi: 10.1172/JCI112705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mattoli S., Miante S., Calabrò F., Mezzetti M., Fasoli A., Allegra L. Bronchial epithelial cells exposed to isocyanates potentiate activation and proliferation of T-cells. Am J Physiol. 1990 Oct;259(4 Pt 1):L320–L327. doi: 10.1152/ajplung.1990.259.4.L320. [DOI] [PubMed] [Google Scholar]
- Nishida T., Nakai S., Kawakami T., Aihara K., Nishino N., Hirai Y. Dexamethasone regulation of the expression of cytokine mRNAs induced by interleukin-1 in the astrocytoma cell line U373MG. FEBS Lett. 1989 Jan 16;243(1):25–29. doi: 10.1016/0014-5793(89)81210-4. [DOI] [PubMed] [Google Scholar]
- Ohtoshi T., Vancheri C., Cox G., Gauldie J., Dolovich J., Denburg J. A., Jordana M. Monocyte-macrophage differentiation induced by human upper airway epithelial cells. Am J Respir Cell Mol Biol. 1991 Mar;4(3):255–263. doi: 10.1165/ajrcmb/4.3.255. [DOI] [PubMed] [Google Scholar]
- Otsuka H., Dolovich J., Richardson M., Bienenstock J., Denburg J. A. Metachromatic cell progenitors and specific growth and differentiation factors in human nasal mucosa and polyps. Am Rev Respir Dis. 1987 Sep;136(3):710–717. doi: 10.1164/ajrccm/136.3.710. [DOI] [PubMed] [Google Scholar]
- Owen W. F., Jr, Rothenberg M. E., Silberstein D. S., Gasson J. C., Stevens R. L., Austen K. F., Soberman R. J. Regulation of human eosinophil viability, density, and function by granulocyte/macrophage colony-stimulating factor in the presence of 3T3 fibroblasts. J Exp Med. 1987 Jul 1;166(1):129–141. doi: 10.1084/jem.166.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pujol J. L., Cosso B., Daurès J. P., Clot J., Michel F. B., Godard P. Interleukin-1 release by alveolar macrophages in asthmatic patients and healthy subjects. Int Arch Allergy Appl Immunol. 1990;91(2):207–210. doi: 10.1159/000235117. [DOI] [PubMed] [Google Scholar]
- Quill H., Gaur A., Phipps R. P. Prostaglandin E2-dependent induction of granulocyte-macrophage colony-stimulating factor secretion by cloned murine helper T cells. J Immunol. 1989 Feb 1;142(3):813–818. [PubMed] [Google Scholar]
- Sanjar S., Smith D., Kings M. A., Morley J. Pretreatment with rh-GMCSF, but not rh-IL3, enhances PAF-induced eosinophil accumulation in guinea-pig airways. Br J Pharmacol. 1990 Jul;100(3):399–400. doi: 10.1111/j.1476-5381.1990.tb15817.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Silberstein D. S., Owen W. F., Gasson J. C., DiPersio J. F., Golde D. W., Bina J. C., Soberman R., Austen K. F., David J. R. Enhancement of human eosinophil cytotoxicity and leukotriene synthesis by biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor. J Immunol. 1986 Nov 15;137(10):3290–3294. [PubMed] [Google Scholar]
- Smith S. M., Lee D. K., Lacy J., Coleman D. L. Rat tracheal epithelial cells produce granulocyte/macrophage colony-stimulating factor. Am J Respir Cell Mol Biol. 1990 Jan;2(1):59–68. doi: 10.1165/ajrcmb/2.1.59. [DOI] [PubMed] [Google Scholar]
- Sun T. T., Green H. Immunofluorescent staining of keratin fibers in cultured cells. Cell. 1978 Jul;14(3):469–476. doi: 10.1016/0092-8674(78)90233-7. [DOI] [PubMed] [Google Scholar]
- Tai P. C., Spry C. J. The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 on the secretory capacity of human blood eosinophils. Clin Exp Immunol. 1990 Jun;80(3):426–434. doi: 10.1111/j.1365-2249.1990.tb03305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thorens B., Mermod J. J., Vassalli P. Phagocytosis and inflammatory stimuli induce GM-CSF mRNA in macrophages through posttranscriptional regulation. Cell. 1987 Feb 27;48(4):671–679. doi: 10.1016/0092-8674(87)90245-5. [DOI] [PubMed] [Google Scholar]
- Wilmott R. W., Kassab J. T., Kilian P. L., Benjamin W. R., Douglas S. D., Wood R. E. Increased levels of interleukin-1 in bronchoalveolar washings from children with bacterial pulmonary infections. Am Rev Respir Dis. 1990 Aug;142(2):365–368. doi: 10.1164/ajrccm/142.2.365. [DOI] [PubMed] [Google Scholar]
- Zucali J. R., Dinarello C. A., Oblon D. J., Gross M. A., Anderson L., Weiner R. S. Interleukin 1 stimulates fibroblasts to produce granulocyte-macrophage colony-stimulating activity and prostaglandin E2. J Clin Invest. 1986 Jun;77(6):1857–1863. doi: 10.1172/JCI112512. [DOI] [PMC free article] [PubMed] [Google Scholar]
