The Journal of Immunology, Vol 142, Issue 6 1922-1928, Copyright © 1989 by American Association of Immunologists

ARTICLES

IFN-beta 2, B cell differentiation factor 2, or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cell lines

R Kirnbauer, A Kock, T Schwarz, A Urbanski, J Krutmann, W Borth, D Damm, G Shipley, JC Ansel and TA Luger
Department of Dermatology II, University of Vienna, Austria.

IL-6, which is also known as IFN-beta 2, hybridoma growth factor, hepatocyte-stimulating factor, and B cell differentiation factor, mediates acute phase responses including fever, has lymphocyte- stimulating capacities, and antiviral activity. IL-6 is produced by monocytes, fibroblasts, certain lymphocytes, and various tumor cells. The present study demonstrates that this multifunctional cytokine is released also by normal human epidermal cells (EC) and human epidermoid carcinoma cell lines (A431, KB). Accordingly, supernatants derived from freshly isolated EC, long term keratinocyte cultures, A431, or KB cells stimulated the proliferation of a hybridoma growth factor/IL-6- dependent plasmacytoma cell line (B9). IL-6 constitutively was produced in the presence of serum proteins. The addition of IL-1 alpha, IL-1 beta, or the tumor promoter PMA significantly enhanced the synthesis and release of EC-derived IL-6 (EC-IL 6). Like monocyte or fibroblast- derived IL-6, EC-IL-6 exhibited Mr microheterogeneity within 21 and 28 kDa. Similarly in Western blotting experiments an antiserum directed against human rIFN-beta 2/IL-6 detected the different Mr forms of EC-IL- 6. Moreover, this antiserum was able to block the B9 cell growth- promoting capacity of EC-IL-6 strongly suggesting that this EC-derived mediator is closely related, if not identical with IL-6. This was further confirmed by Northern blot analysis detecting IL-6 specific mRNA both in long term cultured keratinocytes and A431 cells by hybridization with a cDNA fragment encoding for B cell differentiating factor 2/IL-6. Therefore, in addition to the production of other cytokines as previously reported, EC and in particular keratinocytes also synthesize and release IL-6. This further supports the important regulatory role of the epidermis during the pathogenesis of inflammatory, autoimmune, and neoplastic diseases.

This article has been cited by other articles:

				K. Dvorak, M. Chavarria, C. M. Payne, L. Ramsey, C. Crowley-Weber, B. Dvorakova, B. Dvorak, H. Bernstein, H. Holubec, R. E. Sampliner, et al. Activation of the Interleukin-6/STAT3 Antiapoptotic Pathway in Esophageal Cells by Bile Acids and Low pH: Relevance to Barrett's Esophagus Clin. Cancer Res., September 15, 2007; 13(18): 5305 - 5313. [Abstract] [Full Text] [PDF]

				K. Dvorakova, C. M. Payne, L. Ramsey, H. Holubec, R. Sampliner, J. Dominguez, B. Dvorak, H. Bernstein, C. Bernstein, A. Prasad, et al. Increased Expression and Secretion of Interleukin-6 in Patients with Barrett's Esophagus Clin. Cancer Res., March 15, 2004; 10(6): 2020 - 2028. [Abstract] [Full Text] [PDF]

				K. Scharffetter-Kochanek, H. Lu, K. Norman, N. van Nood, F. Munoz, S. Grabbe, M. McArthur, I. Lorenzo, S. Kaplan, K. Ley, et al. Spontaneous Skin Ulceration and Defective T Cell Function in CD18 Null Mice J. Exp. Med., July 1, 1998; 188(1): 119 - 131. [Abstract] [Full Text] [PDF]