mRNA expression and release of interleukin‐8 induced by serum amyloid A in neutrophils and monocytes

Abstract

The acute phase response is a systemic reaction to inflammatory processes characterized by multiple physiological adaptations, including the hepatic synthesis of acute-phase proteins. In humans, serum amyloid A (SAA) is one of the most prominent of these proteins. Despite the huge increase of serum levels of SAA in inflammation, its biological role remains to be elucidated, even though SAA is undoubtedly active in neutrophils. In a previous study, we reported that SAA induces the release of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-8 from human blood neutrophils. Here, we extend our earlier study, focusing on the effect of SAA on neutrophil IL-8 transcription and on the signaling pathways involved. We demonstrate herein that SAA, in relatively low concentrations (0.4-100 microg/ml) compared with those found in plasma in inflammatory conditions, induces a dose-dependent release of IL-8 from neutrophils. The p38 mitogen-activated protein kinase inhibitor SB 203580 inhibits the IL-8 mRNA expression and the release of protein from neutrophils. The release of IL-8 from SAA-stimulated neutrophils is strongly suppressed by the addition of N-acetyl-l-cysteine, alpha-mercaptoethanol, glutathione, and dexamethasone. SAA also induces IL-8 expression and release from monocytes. In conclusion, SAA appears to be an important mediator of the inflammatory process, possibly contributing to the pool of IL-8 produced in chronic diseases, which may play a role in degenerative diseases.

Increased phosphorylated p38 mitogen-activated protein kinase in COPD lungs

“…Previous studies have demonstrated that p38 MAPK inhibition attenuates chemotaxis [36][37][38][39] and superoxide generation [40], in addition to pro-inflammatory mediator generation [41][42][43] in blood neutrophils. The lack of activated p38 MAPK observed in lung neutrophils makes it unlikely that p38 MAPK inhibition would have any effect on chemotaxis and superoxide generation in lung neutrophils.…”

β2‐Adrenergic receptor regulation of human neutrophil function is sexually dimorphic

“…The inhibitory effect of b 2 -adrenergic receptors may involve the release of a mediator that would impair chemotaxis. For example, it has been shown that IL-8, which is produced by neutrophils (Ribeiro et al, 2003), inhibits neutrophil chemotaxis, in vitro, towards a distant source of IL-8 . We observed that cell culture supernatants collected from isoprenaline-stimulated neutrophils initiated chemotaxis in neutrophils from both males and females.…”

Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes

“…In this respect, interleukin (IL)-8, tumour necrosis factor (TNF)-a and interleukin (IL)-1b are proinflammatory cytokines with a central role in inflammatory processes. IL-8 shows angiogenic, chemotactic and stimulatory activities toward blood cells, providing the recruitment of a great number of neutrophils and other immune cells to the inflammatory site and favouring the appearance of neovascularization [13,14]. TNF-a mediates the systemic effects of inflammation, such as fever, the hepatic release of acute phase proteins and haematopoiesis.…”