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Pro-inflammatory Chemokines (pro-inflammatory + chemokine)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Activation of the Nrf2/antioxidant response pathway increases IL-8 expression

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2005
Xiaolan Zhang
Abstract Oxidant stress can initiate or enhance inflammatory responses during tissue injury, possibly through activation of redox-sensitive chemokines. Because the transcription factor Nrf2 (NF-E2-related factor,2) is responsive to oxidative stress, and induces expression of cytoprotective and antioxidant genes that attenuate tissue injury, we postulated that Nrf2 may also regulate chemokine expression. To test this hypothesis, Nrf2 expression was directly increased in primary human kidney mesangial cells and aortic endothelial cells, or cell lines with an adenoviral construct, and the effects on the pro-inflammatory chemokine interleukin-8 (IL-8) were assessed. Nrf2 expression significantly increased IL-8 mRNA levels and protein secretion. Nrf2 caused only a weak induction of IL-8 transcription, but significantly increased the half-life of IL-8 mRNA. These data demonstrate that activation of the Nrf2/antioxidant response pathway induces expression of IL-8. The dominant mechanism of Nrf2-mediated IL-8 induction is through mRNA stabilization. Considering the evidence that Nrf2 activation is mainly cytoprotective, these observations raise the possibility that under certain circumstances IL-8 may serve an anti-inflammatory role and thereby contribute to the resolution of tissue injury. See accompanying commentary http://dx.doi.org/10.1002/eji.200535489 [source]

Intrasplenic trafficking of natural killer cells is redirected by chemokines upon inflammation

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008
Claude Grégoire
Abstract The spleen is a major homing site for NK cells. How they traffic to and within this site in homeostatic or inflammatory conditions is, however, mostly unknown. Here we show that NK cells enter the spleen through the marginal sinus and home to the red pulp via a pertussis toxin-insensitive mechanism. Upon inflammation induced by poly(I:C) injection or mouse cytomegalovirus infection, many NK cells left the red pulp while others transiently entered the white pulp, predominantly the T cell area. This migration was dependent on both CXCR3 and CCL5, suggesting a synergy between CXCR3 and CCR5, and followed the path lined by fibroblastic reticular cells. Thus, the entry of NK cells in the white pulp is limited by the expression of pro-inflammatory chemokines. This phenomenon ensures the segregation of NK cells outside of the white pulp and might contribute to the control of immunopathology. [source]

Effect of mitogen-activated protein kinases on chemokine synthesis induced by substance P in mouse pancreatic acinar cells

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6 2007
Raina Devi Ramnath
Abstract Substance P, acting via its neurokinin 1 receptor (NK1 R), plays an important role in mediating a variety of inflammatory processes. Its interaction with chemokines is known to play a crucial role in the pathogenesis of acute pancreatitis. In pancreatic acinar cells, substance P stimulates the release of NF,B-driven chemokines. However, the signal transduction pathways by which substance P-NK1 R interaction induces chemokine production are still unclear. To that end, we went on to examine the participation of mitogen-activated protein kinases (MAPKs) in substance P-induced synthesis of pro-inflammatory chemokines, monocyte chemoanractant protein-1 (MCP-I), macrophage inflammatory protein-l, (MIP-l,) and macrophage inflammatory protein-2 (MIP-2), in pancreatic acini. In this study, we observed a time-dependent activation of ERK1/2, c-Jun N-terminal kinase (JNK), NF,B and activator protein-1 (AP-1) when pancreatic acini were stimulated with substance P. Moreover, substance P-induced ERK 1/2, JNK, NF,B and AP-1 activation as well as chemokine synthesis were blocked by pre-treatment with either extracellular signal-regulated protein kinase kinase 1 (MEK1) inhibitor or JNK inhibitor. In addition, substance P-induced activation of ERK 112, JNK, NF,B and AP-1-driven chemokine production were attenuated by CP96345, a selective NK1 R antagonist, in pancreatic acinar cells. Taken together, these results suggest that substance P-NK1 R induced chemokine production depends on the activation of MAPKs-mediated NF,B and AP-1 signalling pathways in mouse pancreatic acini. [source]

An anti-inflammatory oligopeptide produced by Entamoeba histolytica down-regulates the expression of pro-inflammatory chemokines

PARASITE IMMUNOLOGY, Issue 10 2003
Dolores Utrera-Barillas
SUMMARY Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with anti-inflammatory properties that, among others, inhibits the in vitro and in vivo locomotion of human monocytes, sparing polymorphonuclear leucocytes from this effect [hence the name originally given: Monocyte Locomotion Inhibitory Factor (MLIF)]. A synthetic construct of this peptide displays the same effects as the native material. We now added MLIF to resting and PMA-stimulated cells of a human monocyte cell line and measured the effect upon mRNA and protein expression of pro-inflammatory chemokines (RANTES, IP-10, MIP-1,, MIP-1,, MCP-1, IL-8, I-309 and lymphotactin) and the shared CC receptor repertoire. The constitutive expression of these chemokines and the CC receptors was unaffected, whereas induced expression of MIP-1,, MIP-1,, and I-309, and that of the CCR1 receptor , all involved in monocyte chemotaxis , was significantly inhibited by MLIF. This suggests that the inhibition of monocyte functions by MLIF may not only be exerted directly on these cells, but also , and perhaps foremost , through a conglomerate down-regulation of endogenous pro-inflammatory chemokines. [source]

Molecular mechanisms of eosinophil activation in allergic diseases

CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2 2005
J. Chihara
Summary Eosinophils are major effector cells in allergic diseases. These cells possess a variety of membrane receptors that mediate their activation in the presence of pro-inflammatory chemokines such as IL-5, regulated on activation, normal T cell expressed and secreted, eotaxin, and intracellular adhesion molecule (ICAM)-1. ICAM-1 is also implicated in stimulating the production of reactive oxygen species and inducing degranulation of eosinophil granule proteins. Treatment with peroxisome proliferator-activated receptor-, agonist inhibits IL-5-stimulated eosinophil survival and eotaxin-directed eosinophil chemotaxis, suggesting that such agents could serve as a new therapeutic modality for the treatment of allergic diseases. [source]