Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human cytomegalovirus (CMV) infection results in pneumonitis in bone-marrow and lung-transplant recipients. The source of CMV infection contributing to the onset of pneumonitis is unclear, but may involve infection of the lung endothelium in the presence of infiltrating mononuclear cells. Viral infection stimulates the host cell to express chemokines as signals to recruit specific immune cells to the site of injury. CMV encodes a chemokine receptor that may function to reduce host cell expression of chemokines. In the study reported here we found that extracellular concentrations of the chemokine regulated on activation, normal T cell expressed and secreted (RANTES) are depleted during productive infection of primary endothelial cells with CMV strain 4010, an endothelial-adapted strain of CMV. Utilizing adenovirus-transformed human kidney epithelial cells (type 293 cells) that stably express the CMV-encoded chemokine receptor US28, we found that depletion of extracellular RANTES during infection is attributable to US28, which binds and internalizes extracellular RANTES.
 ...
PMID:Depletion of extracellular RANTES during human cytomegalovirus infection of endothelial cells. 1042 97

Infection with the pathogens human cytomegalovirus (HCMV) or Chlamydia pneumonia (CP) is linked to the development of vascular disease, including atherosclerosis. The role of pathogens in vasculopathies has been controversial. However, animal models have demonstrated a direct link between infection with CP and herpesviruses and the development of vascular disease. Clinical studies have shown a direct association of HCMV and CP with the acceleration of vascular disease. This article will review the evidence supporting the role for CP and HCMV in the development of vascular disease and will suggest a potential mechanism for HCMV acceleration of the disease process. Vascular diseases are the result of either mechanical or immune-related injury followed by inflammation and subsequent smooth muscle cell (SMC) proliferation and/or migration from the vessel media to the intima, which culminates in vessel narrowing. A number of in vitro and in vivo models have provided potential mechanisms involved in pathogen-mediated vascular disease. Recently, we have demonstrated that HCMV infection of arterial but not venous SMC results in significant cellular migration in vitro. Migration was dependent on expression of the HCMV-encoded chemokine receptors, US28, and the presence of the chemokines, RANTES or MCP-1. Migration involved chemotaxis and provided the first evidence that viruses may induce migration of SMC toward sites of chemokine production through the expression of a virally encoded chemokine receptor in infected SMC. Because SMC migration into the neointimal space is the hallmark of vascular disease, these observations provide a molecular link between HCMV and the development of vascular disease.
 ...
PMID:Do pathogens accelerate atherosclerosis? 1158 10

Current design strategies for vaccines against certain microbial pathogens, including Chlamydia trachomatis, require the induction and targeting of specific immune effectors to the local sites of infection known as the mucosal effector sites. Chemokines and their receptors are important mediators of leukocyte trafficking and of the controlled recruitment of specific leukocyte clonotypes during host defense against infections and during inflammation. We analyzed the dynamics of chemokine and chemokine receptor expression in genital mucosae during genital chlamydial infection in a murine model to determine how these molecular entities influence the development of immunity and the clearance of infection. A time course study revealed an increase of up to threefold in the levels of expression of RANTES, monocyte chemotactic protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1alpha (MIP-1alpha), and intercellular adhesion molecule type 1 (ICAM-1) after genital infection with the C. trachomatis agent of mouse pneumonitis. Peak levels of expression of RANTES, MCP-1, and MIP-1alpha occurred by day 7 after primary infection, while those of IP-10 and ICAM-1 peaked by day 21. Expression levels of these molecules decreased by day 42 after primary infection, by which time all animals had resolved the infection, suggesting an infection-driven regulation of expression. A rapid upregulation of expression of these molecules was observed after secondary infection. The presence of cells bearing the chemokine receptors CCR5 and CXCR3, known to be preferentially expressed on Th1 and dendritic cells, was also synchronous with the kinetics of immune induction in the genital tract and clearance of infection. Results demonstrated that genital chlamydial infection is associated with a significant induction of chemokines and chemokine receptors that are involved in the recruitment of Th1 cells into the site of infection. Future studies will focus on how selective modulation of chemokines and their receptors can be used to optimize long-term immunity against CHLAMYDIA:
 ...
PMID:Chemokine and chemokine receptor dynamics during genital chlamydial infection. 1179 19

We present an antiviral-immunomodulatory therapeutic strategy involving the chemokine receptor antagonist Met-RANTES, which yields significant survival in the setting of an otherwise fatal respiratory virus infection. In previous work, we demonstrated that infection with the natural rodent pathogen pneumonia virus of mice involves robust virus replication accompanied by cellular inflammation modulated by the CC chemokine macrophage inflammatory protein 1alpha (MIP-1alpha). We found that the antiviral agent ribavirin limited virus replication in vivo but had no impact on morbidity and mortality associated with this disease in the absence of immunomodulatory control. We show here that ribavirin reduces mortality, from 100% to 10 and 30%, respectively, in gene-deleted CCR1(-/-) mice and in wild-type mice treated with the small-molecule chemokine receptor antagonist, Met-RANTES. As MIP-1alpha-mediated inflammation is a common response to several distantly related respiratory virus pathogens, specific antiviral therapy in conjunction with blockade of the MIP-1alpha/CCR1 inflammatory cascade may ultimately prove to be a useful, generalized approach to severe respiratory virus infection and its pathological sequelae in human subjects.
 ...
PMID:Functional antagonism of chemokine receptor CCR1 reduces mortality in acute pneumovirus infection in vivo. 1525 70

Neutrophil hyperactivity contributes to organ failure, whereas hypofunction permits sepsis. The chemokine receptors CXCR1 and CXCR2 are central to polymorphonuclear neutrophil (PMN) function. We prospectively assessed CXCR function and expression in PMNs from trauma patients at high risk for pneumonia and their matched volunteer controls. CXCR2-specific calcium flux and chemotaxis were desensitized by injury, returning toward normal after 1 week. CXCR1 responses were relatively maintained. These defects appeared to be caused by preferential suppression of CXCR2 surface expression. To evaluate potential mechanisms of in vivo chemokine receptor regulation further we studied cross-desensitization of chemokine receptors in normal PMNs. Susceptibility to desensitization was in the order CXCR2 > CXCR1 > formyl peptide or C5a receptors. Trauma desensitizes CXC receptors, with CXCR2 being especially vulnerable. Desensitization is most marked immediately postinjury, generally resolving by Day 7. High-affinity chemoattractant receptors responsible for PMN chemotaxis from bloodstream to tissue appear to be regulated by injury. Receptors for end-target chemoattractants regulate CXCR1 and CXCR2 but resist suppression themselves and respond normally after injury. CXCR2 desensitization occurs before pneumonia, which developed in 44% of these patients. Suppression of high-affinity PMN receptors, like CXCR2, may predispose to pneumonia after trauma or other inflammatory conditions that lead to systemic inflammatory response syndrome.
 ...
PMID:Prospective study of neutrophil chemokine responses in trauma patients at risk for pneumonia. 1561 63

Effector T cells significantly contribute to inflammatory diseases. These cells are recruited into tissue, where they orchestrate an inflammatory response that can either protect against infection or sometimes stimulate human disease. The recruitment of T cells into tissue from the blood and lymphoid compartments is an active process controlled by chemokines and the chemokine receptors expressed on distinct effector T-cell subsets. Thus, the chemokines secreted in the tissue will determine the specific types of T lymphocyte recruited into that tissue based on the chemokine receptors expressed on these cells. It follows that the chemokine receptor profile on T cells isolated from the lungs of patients with inflammatory pulmonary disease will define the subtype of pathogenic T lymphocytes mediating the disease process and will identify the mechanisms that recruit these cells into the lung. This article reviews data from both human and animal studies that define the chemokine receptors involved in the recruitment of T lymphocytes into the lung in various inflammatory pulmonary diseases, including asthma, obliterative bronchiolitis, sarcoidosis, and chronic eosinophilic pneumonia. We then speculate on the potential role of these chemokine receptors in the pathogenesis of these disorders and potential novel therapeutic approaches suggested by these data.
 ...
PMID:Pathogenic T-cell recruitment into the airway in human disease. 1646 4

Adoptive transfer of CD4+CD25+ regulatory T cells has been shown to have therapeutic effects in animal models of autoimmune diseases. Chemokines play an important role in the development of autoimmune diseases in animal models and humans. The present study was performed to investigate whether the progression of organ-specific autoimmune diseases could be reduced more markedly by accumulating chemokine receptor-expressing CD4+CD25+ regulatory T cells efficiently in target organs in MRL/MpJ-lpr/lpr (MRL/lpr) mice. CD4+CD25+Foxp3+ T cells (Treg cells) and CD4+CD25+Foxp3+ CCR2-transfected T cells (CCR2-Treg cells) were transferred via retro-orbital injection into 12-week-old MRL/lpr mice at the early stage of pneumonitis and sialadenitis, and the pathological changes were evaluated. Expression of monocyte chemoattractant protein-1 (MCP-1)/CCL2 was observed in the lung and submandibular gland of the mice and increased age-dependently. The level of CCR2 expression and MCP-1 chemotactic activity of CCR2-Treg cells were much higher than those of Treg cells. MRL/lpr mice to which CCR2-Treg cells had been transferred showed significantly reduced progression of pneumonitis and sialadenitis in comparison with MRL/lpr mice that had received Treg cells. This was due to more pronounced migration of CCR2-Treg cells and their localization for a longer time in MCP-1-expressing lung and submandibular gland, resulting in stronger suppressive activity. We prepared chemokine receptor-expressing Treg cells and demonstrated their ability to ameliorate disease progression by accumulating in target organs. This method may provide a new therapeutic approach for organ-specific autoimmune diseases in which the target antigens remain undefined.
 ...
PMID:Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4+CD25+ regulatory T cells in MRL/lpr mice. 1728 25

Chemokine (C-C motif) Receptor 5 (CCR5) is a chemokine receptor that regulates immune cell recruitment in inflammation and serves as a coreceptor for human immunodeficiency virus (HIV). A human CCR5 coding deletion (termed delta-32) results in strong resistance to HIV infection, and sequence variants in CCR5 regulatory regions have been implicated in delayed progression to acquired immune deficiency syndrome. Both ovine progressive pneumonia virus (OPPV), also known as maedi-visna, and HIV are macrophage-tropic lentiviruses, have similar genomic structures, and cause lifelong persistent host infection, suggesting CCR5 may have a role in regulating OPPV provirus levels. Therefore, the ovine CCR5 genomic sequence was determined, and sequence variants were obtained from the open reading frame and surrounding regulatory sites. One CCR5 variant contained a 4-base deletion within a binding site for octamer transcription factors in the promoter region. A test for differential transcription from each allele in heterozygous animals showed a 3.9-fold transcription difference (P < 0.0001). OPPV proviral levels were also measured in 351 naturally exposed Rambouillet, Polypay and Columbia sheep. Deletion homozygotes showed reduced OPPV proviral levels among these animals (P < 0.01). The association of this CCR5 promoter deletion with OPPV levels will need to be validated in additional populations before the deletion can be recommended for widespread use in marker-assisted selection. However, because of the large impact on transcription and because CCR5 has roles in inflammation, recruitment of effector cells, and cell-mediated immunity, this deletion may play a role in the control of infections of many diverse pathogens of sheep.
 ...
PMID:Common promoter deletion is associated with 3.9-fold differential transcription of ovine CCR5 and reduced proviral level of ovine progressive pneumonia virus. 1939 12

The study included 243 patients with acute community-acquired pneumonia and 173 healthy subjects. The following candidate loci were used to investigate genetic variability: 3 sites of CYP1A1, GSTM1, GSTT1, GSTP1, ACE gene of the rennin-angiotensin system, chemokine receptor gene CCR5. Enhanced predisposition to pneumonia was shown to be characteristic of homozygotes in deletion at the ACE locus (OR = 1.8; p = 0.013), carriers of normal alleles of the GSTM1 locus (OR = 1.7; p = 0.010), and homozygotes in allele 606T of the CYP1A1 gene (OR = 1.6; p = 0.020).
 ...
PMID:[Genetic study of predisposition to community-acquired pneumonia]. 2231 1

The term "interstitial pneumonia with autoimmune features" (IPAF) has been recently proposed. We here investigate the clinical characteristics of IPAF and evaluate the clinical implications of CXCL1-CXCR2 axis in IPAF. An increased plasma level of CXCL1 was exhibited in IPAF compared to idiopathic interstitial pneumonia (IIP), chronic obstructive pulmonary disease (COPD), and healthy controls. Additionally, plasma CXCL1 levels were clinically associated with diffusing capacity of the lungs for carbon monoxide (DLCO), erythrocyte sedimentation rate (ESR), and involved parenchyma extension in IPAF. Furthermore, circulating CXCL1 levels were highest in IPAF patients with acute exacerbations. CXCR2, the chemokine receptor for CXCL1, was readily observed in inflammatory aggregates and endothelial cells in IPAF lungs, but was lower in IIP lungs and healthy lungs. Interestingly, increased CXCL1 concentrations in BALF paralleled neutrophil counts in IPAF. Overall, the plasma concentrations of CXCL1 indicated the disease activity and prognosis in IPAF. Thus, the CXCL1/CXCR2 axis appears to be involved in the progression of IPAF.
 ...
PMID:Clinical Association of Chemokine (C-X-C motif) Ligand 1 (CXCL1) with Interstitial Pneumonia with Autoimmune Features (IPAF). 2795 46


1 2 Next >>