Interleukins tumor promoters

Lee, W.Y, Fischer, S.M., Butler, A.P. Locniskar, M.F. (1993) Modulation of interleukin-la mRNA expression in mouse epidermis by tumor promoters and antagonists. Mol. Carcinog., 7, 26-35... 

Katiyar, S.K. et al.. Inhibition of 12-0-tetradecanoylphorbol-13-acetate and other skin tumor-promoter-caused induction of epidermal interleukin-1 alpha ruRNA and protein expression in SENCAR mice by green tea polyphenols, J. Investig. Dermatol., 105, 394, 1995. 

Azzarone B, Pottin-Clemenceau C, et al. Are interleukin-2 and interleuldn-15 tumor promoting factors for human non-hematopoietic cells Eur Cytokine Netw 1996 7 27-36. 

Regarding chronic effects, OA and DTX-1 have been shown to be potent tumor promoters, and given that the stomach, small intestine, and colon have binding sites of OA, this could be implicated in the growth of gastrointestinal tumors [17,18]. Mutagenic [19] and immunotoxic effects due to a marked suppression of interleukin-1 (lL-1) production have also been described [20],... 

Cytokines are known to play an important role in a variety of physiological and pathological processes, including inflammation, wound healing, immunity, and hematopoiesis. Interleukin-la (IL-la) plays an important role in both immune and inflammatory reactions, and it has been shown to be induced in response to various skin tirmor promoters (Katiyar et al., 1995b). We conducted studies to assess whether pretreatment of the animal with GTP can afford preventive effects against tumor-promoter-caused induction of IL-la expression in the mttrine skin model system. 

Katiyar, S.K., Agarwal, R., Koiman, N.J., Rupp, C.O., and Mukhtar, H., Inhibition of tumor promoter-caused induction of interleukin-1 (IL-l)-alpha, tumor necrosis factor (TNF)-alpha, and ornithine decarboxylase (ODC) gene expression in SENCAR mouse skin by tea polyphenols, Proc. Am. Assoc. Cancer Res., 36, 594,1995b. 

Activator protein-1 (AP-1) is an important transcription factor that figures in the inflammation response. AP-1 is a dimeric complex of the protooncoproteins jun and fos that is induced by growth factors, cytokines, tumor promoters, and sunlight [39]. Activation of AP-1 increases the transcription of cytokines, such as interleukin-2, and certain matrix metalloproteinases [40]. In the presence of t-RA, RARs can inhibit the actions of AP-1. Reciprocally, elevated expression of either the jun or fos components of AP-1 can prevent activation of RAREs by RARs. This repression of gene transcription, called transrepression, is a well-known mechanism for crosstalk between retinoid receptors and AP-1 [41-43]. The molecular mechanism of transrepression described for in vitro systems is dependent on the presence of t-RA and is believed to involve direct or indirect protein-protein interactions between retinoid receptors and AP-1 components (jun and fos), and/or competition between retinoid receptors and AP-1 for a common factor (or factors) required for their activities [42, 43]. However, this phenomenon studied in the context of photoaging of human skin in vivo has revealed a novel mechanism. 

Anasagasti, M.J., Alvarez, A., Martin, J.J., Mendoza, L., and Vidal-Vanaclocha, F. (1997a). Sinusoidal endothelium release of hydrogen peroxide enhances very late antigen-4-mediated melanoma cell adherence and tumor cytotoxicity during interleukin-1 promotion of hepatic melanoma metastasis in mice. Hepatology 25(4), 840-846. 

Multiple factors play a role in the development of AOM. Viral infection of the nasopharynx impairs eustachian tube function and causes mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. Children are predisposed to AOM because their eustachian tubes are shorter, more flaccid, and more horizontal than adults, which make them less functional for drainage and protection of the middle ear from bacterial entry. Clinical signs and symptoms of AOM are the result of host immune response and damage to cells caused by inflammatory mediators such as tumor necrosis factor and interleukins that are released from bacteria.4... 

F12. Flores, E. A., Bistrian, B. R., Pomposelli, J. J., Dinarello, C. A., Blackburn, G. L, and Istfan, N. W., Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat. A synergistic effect with interleukin l.J. Clin. Invest. 83, 1614-1622 (1989). 

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