Monocyte chemoattractant protein-1 influences trauma-hemorrhage-induced distal organ damage via regulation of keratinocyte-derived chemokine production

2007 ◽  
Vol 292 (3) ◽  
pp. R1110-R1116 ◽  
Author(s):  
Michael Frink ◽  
Ailing Lu ◽  
Bjoern M. Thobe ◽  
Ya-Ching Hsieh ◽  
Mashkoor A. Choudhry ◽  
...  
Keyword(s):  
Neutrophil Infiltration ◽  
Organ Damage ◽  
Sham Operation ◽  
Neutrophil Accumulation ◽  
Edema Formation ◽  
Chemokine Production ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Control Serum

Leukocyte infiltration, mediated by chemokines, is a key step in the development of organ dysfunction. Lung and liver neutrophil infiltration following trauma-hemorrhage is associated with upregulation of monocyte chemoattractant protein-1 (MCP-1). Because MCP-1 is not a major attractant for neutrophils, we hypothesized that MCP-1 influences neutrophil infiltration via regulation of keratinocyte-derived chemokines (KC). To study this, male C3H/HeN mice were pretreated with MCP-1 antiserum or control serum and subjected to trauma-hemorrhage or sham operation. Animals were killed 4 h after resuscitation. One group of trauma-hemorrhage mice receiving MCP-1 antiserum was also treated with murine KC during resuscitation. Plasma levels and tissue content of MCP-1 and KC were determined by cytometric bead arrays. Immunohistochemistry was performed to determine neutrophil infiltration; organ damage was assessed by edema formation. Treatment with MCP-1 antiserum significantly decreased systemic, lung, and liver levels of MCP-1 and KC following trauma-hemorrhage. This decrease in MCP-1 levels was associated with decreased neutrophil infiltration and edema formation in lung and liver following trauma-hemorrhage. Restitution of KC in mice treated with MCP-1 antiserum restored tissue neutrophil infiltration and edema. These results lead us to conclude that increased levels of MCP-1 cause neutrophil accumulation and distant organ damage by regulating KC production during the postinjury inflammatory response.

17β-Estradiol inhibits keratinocyte-derived chemokine production following trauma-hemorrhage

2007 ◽  
Vol 292 (2) ◽  
pp. L585-L591 ◽  
Author(s):  
Michael Frink ◽  
Bjoern M. Thobe ◽  
Ya-Ching Hsieh ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Kupffer Cell ◽  
Neutrophil Infiltration ◽  
Organ Damage ◽  
Sham Operation ◽  
Myeloperoxidase Activity ◽  
Edema Formation ◽  
Chemokine Production ◽  
Cell Production ◽  
Tnf Α ◽  
17Β Estradiol

Neutrophil infiltration is a key step in the development of organ dysfunction following trauma-hemorrhage (T-H). Although we have previously shown that 17β-estradiol (E2) prevents neutrophil infiltration and organ damage following T-H, the mechanism by which E2 inhibits neutrophil transmigration remains unknown. We hypothesized that E2 prevents neutrophil infiltration via modulation of keratinocyte-derived chemokine (KC), a major attractant for neutrophils. To examine this, male C3H/HeN mice were subjected to T-H or sham operation and thereafter resuscitated with Ringer lactate and E2 (1 mg/kg body wt) or vehicle. Animals were killed 2 h after resuscitation, and Kupffer cells were isolated. Plasma levels and Kupffer cell production capacities of KC, TNF-α, and IL-6 were determined by BD Cytometric Bead Arrays; lung mRNA expression of KC was measured with real-time PCR; myeloperoxidase activity assays were performed to determine neutrophil infiltration, and organ damage was assessed by edema formation. Treatment with E2 decreased systemic levels and restored Kupffer cell production of KC, TNF-α, and IL-6, as well as KC gene expression and protein in the lung. This was accompanied with a decrease in neutrophil infiltration and edema formation in the lung. These results suggest that E2 prevents lung neutrophil infiltration and organ damage in part by decreasing KC during posttraumatic immune response.

Downregulation of migration inhibitory factor is critical for estrogen-mediated attenuation of lung tissue damage following trauma-hemorrhage

2007 ◽  
Vol 292 (5) ◽  
pp. L1227-L1232 ◽  
Author(s):  
Ya-Ching Hsieh ◽  
Michael Frink ◽  
Chi-Hsun Hsieh ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Lung Injury ◽  
Migration Inhibitory Factor ◽  
Tissue Damage ◽  
Neutrophil Infiltration ◽  
Organ Damage ◽  
Inhibitory Factor ◽  
Sham Operation ◽  
Protective Effects ◽  
Chemokine Production ◽  
Monocyte Chemoattractant Protein 1

Although studies have shown that 17β-estradiol (E2) prevents neutrophil infiltration and organ damage following trauma-hemorrhage, the mechanism by which E2inhibits neutrophil transmigration remains unknown. Macrophage migration inhibitory factor (MIF) is thought to play a central role in exacerbation of inflammation and is associated with lung injury. MIF regulates the inflammatory response through modulation of Toll-like receptor 4 (TLR4). Activation of TLR4 results in the release of proinflammatory cytokines and chemokines, which induce neutrophil infiltration and subsequent tissue damage. We hypothesized that E2mediates its salutary effects in the lung following trauma-hemorrhage via negative regulation of MIF and modulation of TLR4 and cytokine-induced chemotaxis. C3H/HeOuJ mice were subjected to trauma-hemorrhage (mean blood pressure 35 ± 5 mmHg for ∼90 min, then resuscitation) or sham operation. Mice received vehicle, E2, or E2in combination with recombinant mouse MIF protein (rMIF). Trauma-hemorrhage increased lung MIF and TLR4 protein levels as well as lung and systemic levels of cytokines/chemokines. Treatment of animals with E2following trauma-hemorrhage prevented these changes. However, administration of rMIF protein with E2abolished the E2-mediated decrease in lung TLR4 levels, lung and plasma levels of IL-6, TNF-α, monocyte chemoattractant protein-1, and keratinocyte-derived chemokine (KC). Administration of rMIF protein also prevented E2-mediated reduction in neutrophil influx and tissue damage in the lungs following trauma-hemorrhage. These results suggest that the protective effects of E2on lung injury following trauma-hemorrhage are mediated via downregulation of lung MIF and TLR4-induced cytokine/chemokine production.

Cyclopentenone Prostaglandins Inhibit Cytokine-Induced NF-κB Activation and Chemokine Production by Human Mesangial Cells

2001 ◽  
Vol 12 (8) ◽  
pp. 1659-1667
Author(s):  
BRAD H. ROVIN ◽  
LING LU ◽  
ANNA COSIO
Keyword(s):  
Inflammatory Response ◽  
Mesangial Cells ◽  
Gene Activation ◽  
Chemokine Production ◽  
Human Mesangial Cells ◽  
Renal Inflammation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Cyclopentenone Prostaglandins

Abstract. In the kidney an uncontrolled inflammatory response to an acute insult may lead to chronic inflammation, permanent tissue damage, and progressive renal insufficiency. Resolution of acute inflammation likely is dependent on endogenous regulatory mechanisms activated in parallel with mediators of renal inflammation. These mechanisms are postulated to attenuate the renal expression of proinflammatory cytokines, including the chemokines responsible for recruiting leukocytes to the kidney, thus facilitating the transition from inflammation to healing. To understand the regulation of the inflammatory response within the kidney, the effects of anti-inflammatory J series cyclopentenone prostaglandins on chemokine production by human mesangial cells were examined. Treatment of mesangial cells with prostaglandin J2and 15-deoxy-Δ12,14-prostaglandin J2blocked interleukin-1β—induced monocyte chemoattractant protein-1 mRNA expression and protein production. This correlated with failure of the transcription factor nuclear factor-κB (NF-κB) to translocate to the nucleus and bind to its recognition motif, a step required for cytokine-induced monocyte chemoattractant protein-1 gene activation. NF-κB failed to translocate because the cyclopentenone prostaglandins attenuated degradation of the NF-κB inhibitor IκB-α. These data suggest that certain prostaglandins can limit the extent of renal chemokine expression and thus may have an important role in resolving renal inflammation.

scholarly journals Protease-activated receptor 1 activation is necessary for monocyte chemoattractant protein 1–dependent leukocyte recruitment in vivo

2008 ◽  
Vol 205 (8) ◽  
pp. 1739-1746 ◽  
Author(s):  
Daxin Chen ◽  
Adam Carpenter ◽  
Joel Abrahams ◽  
Rachel C. Chambers ◽  
Robert I. Lechler ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Mouse Heart ◽  
Protease Activated Receptors ◽  
Chemokine Production ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cell Recruitment ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Protease Activated Receptor 1

Thrombin, acting through a family of protease-activated receptors (PARs), is known to amplify inflammatory responses, but the in vivo importance of PARs in inflammation is not fully appreciated. In a mouse heart-to-rat transplant model, where it is possible to distinguish graft (mouse) from systemic (rat) chemokines, we show that donor PAR-1 is required to generate the local monocyte chemoattractant protein (MCP)-1 needed to recruit rat natural killer cells and macrophages into the hearts. We have confirmed the importance of this mechanism in a second model of thioglycollate-induced peritonitis and also show that PAR-1 is important for the production of MCP-3 and MCP-5. Despite the presence of multiple other mediators capable of stimulating chemokine production in these models, these data provide the first evidence that thrombin and PAR activation are required in vivo to initiate inflammatory cell recruitment.

Sign in / Sign up

Export Citation Format

Share Document