Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases

Abstract

Fifteen years have passed since the first description of interleukin (IL)-8/CXCL8 as a potent neutrophil chemotactic factor. Accumulating evidence has demonstrated that various types of cells can produce a large amount of IL-8/CXCL8 in response to a wide variety of stimuli, including proinflammatory cytokines, microbes and their products, and environmental changes such as hypoxia, reperfusion, and hyperoxia. Numerous observations have established IL-8/CXCL8 as a key mediator in neutrophil-mediated acute inflammation due to its potent actions on neutrophils. However, several lines of evidence indicate that IL-8/CXCL8 has a wide range of actions on various types of cells, including lymphocytes, monocytes, endothelial cells, and fibroblasts, besides neutrophils. The discovery of these biological functions suggests that IL-8/CXCL8 has crucial roles in various pathological conditions such as chronic inflammation and cancer. Here, an overview of its protein structure, mechanisms of production, and receptor system will be discussed as well as the pathophysiological roles of IL-8/CXCL8 in various types of lung pathologies.

Opposite roles of neutrophils and macrophages in the pathogenesis of acetaminophen‐induced acute liver injury

“…On the contrary, we observed that APAP-induced liver injury was markedly attenuated in CXCR2-KO mice with reduced neutrophil infiltration, compared with WT mice, in line with previous reports that CXCR2-KO mice exhibited attenuated neutrophil infiltration in various disease models [16][17][18][19][20][21][22][23][24][25][26][27]. Indeed, Hogaboam and colleagues [38] observed that only a low level of CXCR2 was expressed on untreated hepatocytes and that APAP could enhance CXCR2 protein expression only transiently with a time lag.…”

“…In contrast, Smith and his colleagues [16] demonstrated that rats treated by anti-neutrophil serum exhibited an enhanced resistance to APAP-induced hepatotoxicity, although they did not explore its mechanisms in detail. Thus, there still remain controversies on the pathogenic roles of neutrophils in APAP-induced liver injury.Neutrophil recruitment is regulated by CXC chemokine ligands (CXCL), murine KC/CXCL1, and macrophage inflammatory protein (MIP)-2/CXCL2 [17,18]. Several lines of evidence demonstrated that the recruitment of neutrophils was significantly reduced in some disease models using mice lacking CXC chemokine receptor 2 (CXCR2), a receptor for CXCL1 and CXCL2 [19][20][21][22][23][24][25][26].…”

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

“…In addition, bronchial epithelium also directly contributes to immune responses by secreting bioactive substances when exposed to pathogens or stimulation by inflammatory mediators [8]. Among them, interleukin (IL)-8, a member of the CXC chemokine family, plays a pivotal role in regulating neutrophil and monocyte chemotaxis toward sites of infection, and in inducing airway inflammation [9,10]. The presence of microorganisms such as M. catarrhalis in the lower respiratory tract of COPD patients has been found to increase IL-8 release in bronchoalveolar lavage of COPD patients, which is associated with disease progression [11][12][13].…”

“…Transcriptional regulation of IL-8 is controlled by a tight regulatory signalling network, most importantly involving the nuclear factor (NF)-kB. NF-kB comprises a family of Rel proteins that are normally retained in the cytoplasm by binding to NF-kB inhibitors (IkBs) [9,14]. Following cellular activation, phosphorylation of IkBa results in its ubiquitination and proteolysis, which lead to nuclear translocation and binding to the IL-8 kB-binding site within the il8 promoter [14].…”

Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

“…CXCR1 and CXCR2 are G protein receptors and have a high affinity for chemokines that are glutamine-leucine--arginine positive (Mukaida 2003, Kim et al 2011). These chemokines have been detected in several human and equine tissues affected by inflammatory conditions associated with severe neutrophil infiltration (Franchini et al 2000, Giustizieri et al 2001, Ainsworth et al 2006, Woodman et al 2006.…”