Regulation of Interleukin-8 by Interleukin-10 and Transforming Growth Factor β in Human Monocytes Infected withMycobacterium bovis

Abstract

Recent studies indicate that interleukin 8 (IL-8) production contributes to the host immune responses against mycobacterial infection. In this study, we were interested to determine whether induction of IL-8 in human monocytes infected with Mycobacterium bovis was regulated by other monocyte-derived cytokines important in antimycobacterial immunity: IL-10 and transforming growth factor ␤ (TGF-␤). Here, we report that IL-10 reduced, in a graded and significant manner, IL-8 production by M. bovis-infected human monocytes. Additionally, the specificity of the observed inhibition was further confirmed, since the addition of an anti-IL-10 neutralizing antibody completely reversed the inhibitory effect. In contrast, addition or neutralization of TGF-␤ appeared to have no significant effect on M. bovis-induced IL-8 secretion by human monocytes, whereas CD40 expression on M. bovis-infected monocytes was significantly inhibited by this cytokine. This was consistent with the finding by the reverse transcription-PCR method that pretreatment with IL-10, but not TGF-␤, potently inhibited IL-8 mRNA levels. Interestingly, neutralization of endogenous IL-10 did not significantly alter IL-8 secretion, suggesting that induction of IL-8 was not significantly affected by coexpression of IL-10 during infection of human monocytes with M. bovis. Collectively, these data indicate that IL-8 production may be regulated when human monocytes are exposed to IL-10 prior to activation with M. bovis BCG. These data will aid in our understanding of the mechanisms involved in regulating the protective immune response to stimulation with M. bovis BCG.

Plasma IL‐8 signature correlates with pain and depressive symptomatology in patients with burning mouth syndrome: Results from a pilot study

“…Given that plasma IL‐8:IL‐10 ratio positively correlates with measures of pain and depression, our data support the hypothesis that the balance between pro‐ and anti‐inflammatory cytokines/chemokines may potentially reflect the clinical manifestations of disease in BMS. Furthermore, IL‐10 can negatively regulate IL‐8 expression in immune cells, and our findings indicating a high IL‐8 to IL‐10 ratio in BMS plasma support this. Future studies aimed at identifying the impact of BMS on immune cell profiles in blood samples will be required in order to address this question directly.…”

Latent effects of fibronectin, α5β1 integrin, αVβ5 integrin and the cytoskeleton regulate pancreatic carcinoma cell IL-8 secretion

“…This suggests that although α 5 β 1 can stimulate cytoskeletal organisation and thereby limit IL-8 secretion, the cytoskeleton must influence secretion by at least one additional mechanism, consistent with the finding that fibronectin maintains an inhibitory effect despite cytochalasin treatment. A range of growth factors and cytokines are known to signal via the cytoskeleton and some, for example, IL-10 and TGF β , are known to inhibit IL-8 secretion (de Waal Malefyt et al , 1991; Mendez-Samperio et al , 2002). These cytokines have also been implicated in pancreatic carcinogenesis (Bellone et al , 1999; Nicolas and Hill, 2003).…”

Dual-parallel inhibition of IL-10 and TGF-β1 controls LPS-induced inflammatory response via NF-κB signaling in grass carp monocytes/macrophages

“…TGF-b1 downregulates the release of NO and superoxide ion, and inhibits the mRNA level of inos in activated macrophages [12]. In Mycobacterium bovis infected human monocytes, IL-10 but not TGF-b1 regulates IL-8 production [13]. In view of the pivotal role of NF-kB signaling pathway in mediating the expression of IL-1b, TNF-a, adhesion molecules, IL-8 and iNOS during inflammation [14,15], the effect of IL-10 and TGF-b1 on NF-kB signaling activation has been determined.…”