TNF-a-gene expression

Anti-arthritic effect. Oral administration of AJA, a cannabinoid acid devoid of psychoactivity, reduced joint tissue damage in rats with adjuvant arthritis. Peripheral blood monocytes (PBM) and synovial fluid monocytes (SFM) were isolated from healthy subjects and patients with inflammatory arthritis, respectively, treated with AJA (0-30 mM) in vitro, and then stimulated with lipopolysaccharide. Cells were harvested for messenger RNA (mRNA), and supernatants were collected for cytokine assay. Addition of AJA to PBM and SFM in vitro reduced both steady-state levels of interleukin-ly (IL-ly) mRNA and secretion of IL-ly in a concentration-dependent manner. Suppression was maximal (50.4%) at 10 mM AJA (p < 0.05 vs untreated controls, n = 7). AJA did not influence tumor necrosis factor-a (TNF-a) gene expression in or secretion from PBM . 

In mouse splenocytes and human peripheral blood mononuclear cells treated with an extract of shiitake, the expression levels of IL-2 and TNF-a genes were augmented in both sets of cells. The production of IL-2 was augmented in the mouse splenocytes, and the production of TNF-a was augmented in murine peritoneal exudate macrophages. The production of IL-2 and TNF-a was augmented in the human mononuclear cells (Liu et al. 1998). 

Interleukin-6 (IL-6) is a small polypeptide with a molecular mass of 26 kDa (see Table 2). IL-6 can be induced in various cell types, including fibroblasts, macrophages/monocytes, epithelial cells, T cells, B cells, and diverse tumor cells (L4). TNF, IL-1, and LPS can stimulate IL-6 gene expression in macrophages/monocytes and fibroblasts. In vivo studies showed that systemic administration of TNF, LPS, and IL-1 was followed by a rapid induction of circulating IL-6 (B49, J2). Also, endothelin (ET) at concentrations observed pathophysiolog-ically may trigger production of IL-6 (Ml7). 

Continuing with the theme of COX-2 regulation, ERK and p38, but not JNK, are involved in trichothecene-induced transactivation of this gene.17-28 p38 also appears to mediate trichothecene-induced mRNA stability. DON-induced TNF-a expression is similarly regulated.30... 

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