Synthesis of interleukin 1 beta and interleukin 6 in human lymphocytes is stimulated by tributyltin

Abstract

Tributyltin (TBT) is a widespread environmental contaminant that is present in human blood and other tissues. It has been shown to disrupt the immune function of human natural killer (NK) cells and to alter the secretion of a number of pro-inflammatory cytokines from immune cells. Secretion of both interleukin 1β (IL-1β) and interleukin 6 (IL-6) from human lymphocytes can be increased dependent upon the level of TBT exposure. This study shows that the TBT-induced increases in secretion of both cytokines are due to TBT-induced increases in the synthesis of these proteins and not simply because of the release of pre-existing cytokine. Furthermore, the data indicate that these TBT-induced increases in IL-1β and IL-6 synthesis require MAP kinase signaling pathways. Additionally, elevated synthesis of IL-1β and IL-6 seen at the highest exposures to TBT (200, 200, 50 nM) were accompanied by increases in the mRNA for these cytokines. TBT-induced increases in IL-1β and IL-6 mRNAs were also shown to be dependent on MAP kinase signaling. The study suggests that TBT has the capacity to increase immune cell production of these 2 important pro-inflammatory cytokines and that this increase is in part explained by increased mRNA for the cytokines.

NF-κB blockade during short-terml-NAME and salt overload strongly attenuates the late development of chronic kidney disease

“…Influx of T lymphocytes into the kidneys may be important in the pathogenesis of hypertension (30). In addition, abundant evidence has been obtained in recent years that lymphocytes are able to secrete inflammatory cytokines (7) and that T cell subtypes such as T helper (Th)1 and Th17, as well as associated cytokines such as IL-2, interferon-␥, and IL-17, participate in the pathogenesis of inflammation in hypertension (28), diabetic kidney disease (25), glomerulonephritis (5,40), and, in particular, in the L-NAME ϩ HS model (23). Of interest, proinflammatory cytokines such as IL-6 and IL-1␤, which have been associated with the NF-B and NLRP3 pathways, respectively, can be synthesized by T cells (7).…”

Exposures to the environmental contaminants pentachlorophenol and dichlorodiphenyltrichloroethane increase production of the proinflammatory cytokine, interleukin‐1β, in human immune cells

“…These results can be compared with those seen with the organotin contaminant, tributylin (TBT). TBT like PCP and DDT appears to rely predominantly on the p38 pathway, and has some requirement for the p44/42 pathway to stimulate IL‐1β production in immune cells (Brown, Hamza, Boules, Wang, & Whalen, ). Additionally, activation of p38 by DDT and its metabolites leads to altered gene expression in a human embryonic kidney epithelial cell line and in an endometrial cell line (Frigo et al, ) and apoptosis in cultured rat Sertoli cells (Song, Shi, Yu, Wang, & Yang, ).…”

“…Additionally, TBT can significantly increase the production of IL‐1β in lymphocytes. Production begins to increase after the 6‐hour exposure and continued to increase after the 24‐hour exposure (Brown et al, ). TBT's ability to alter production can be partially attributed to increases in mRNA for IL‐1β (Brown et al, ).…”

“…Production begins to increase after the 6‐hour exposure and continued to increase after the 24‐hour exposure (Brown et al, ). TBT's ability to alter production can be partially attributed to increases in mRNA for IL‐1β (Brown et al, ). Owing to the importance of IL‐1β in normal immune function and in the development of chronic inflammation leading to certain disease states such as rheumatoid arthritis, it is important to understand the role of the array of contaminants that humans are exposed to in altering appropriate levels of these proteins.…”

Endocrine Disruptor Compounds—A Cause of Impaired Immune Tolerance Driving Inflammatory Disorders of Pregnancy?

“…EDCs also have significant impact on the production of inflammatory cytokines by NK cells, with several studies clearly demonstrating NK cells exhibit non-monotonic dose responses (110). Inflammatory cytokines such as TNF, IL1-b, IL-6 and IFN-g were increased in response to low-dose exposure to various EDCs including TBT and dibutylin (DBT) (158)(159)(160). In the case of TBT-induced pro-inflammatory cytokines this was mediated through the activation of extracellular-signal-regulated kinase 1/2 and p38 kinase pathways (158)(159)(160).…”