Animals ; Chemokine CCL20 ; Chemokine CXCL10 ; Chemokines, CC ; biosynthesis ; Chemokines, CXC ; biosynthesis ; Liver ; metabolism ; Liver Transplantation ; Macrophage Inflammatory Proteins ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Transplantation, Homologous

BACKGROUND: Psoriatic keratinocytes express CXC chemokines like IL-8 and GRO-alpha, and CC chemokines like MCP-1 and RANTES, which have a significant role in the accumulation of inflammatory cells in psoriatic skin and both CXCR1 and CXCR2 receptors are also expressed in psoriatic keratinocytes, which suggests that IL-8 and GRO-alpha could have a role in the characteristic epidermal changes through binding to their receptors in psoriatic keratinocytes. OBJECTIVE: The purpose is to understand the pathogenetic mechanisms of psoriasis by comparing immunoreactivity of various chemokines and chemokine receptors between lesional and non-lesional skin of psoriasis. METHODS:We have performed immunohistochemical studies with mouse anti-human IL-8, mouse anti-human GRO, anti-huamn MCP-1, mouse anti-human RANTES, anti-human CDw 128 IL-8RA/ CXCR1, and anti-human IL-8RB/CXCR2 for lesional and non-lesional skin of ten psoriatic patients. RESULTS: 1.Immunohistochemical reactivity for IL-8 is stronger in lesional epidermis than non-lesional epidermis(p<0.05) and immunohistochemical reactivity for GRO-alpha is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 2.Immunohistochemical reactivity for MCP-1 is stronger in lesional epidermis than non-lesional epidermis(p<0.05), and immunohistochemical reactivity for RANTES is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 3.Immunohistochemical reactivity for CXCR1 is stronger in lesional epidermis than non-lesional epidermis(p<0.05) and immunohistochemical reactivity for CXCR2 is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 4.Immunofluorescent staining reveals positive finding in epidermis of lesional psoriasis, but negative finding in CXCR2. CONCLUSION: These results suggest that psoriatic keratinocytes express CXC chemokines like IL-8 and GRO-alpha, and CC chemokines like MCP-1 and RANTES, which have a significant role in the accumulation of inflammatory cells in psoriatic skin and that both CXCR1 and CXCR2 receptors are also expressed in psoriatic keratinocytes, which suggests that IL-8 and GRO-alpha could have a role in the characteristic epidermal changes through binding to their receptors in psoriatic keratinocytes.
Animals ; Chemokine CCL5 ; Chemokines* ; Chemokines, CC ; Chemokines, CXC ; Epidermis ; Humans ; Interleukin-8 ; Keratinocytes ; Mice ; Psoriasis* ; Receptors, Chemokine* ; Receptors, Interleukin-8B ; Skin

BACKGROUND: Psoriatic keratinocytes express CXC chemokines like IL-8 and GRO-alpha, and CC chemokines like MCP-1 and RANTES, which have a significant role in the accumulation of inflammatory cells in psoriatic skin and both CXCR1 and CXCR2 receptors are also expressed in psoriatic keratinocytes, which suggests that IL-8 and GRO-alpha could have a role in the characteristic epidermal changes through binding to their receptors in psoriatic keratinocytes. OBJECTIVE: The purpose is to understand the pathogenetic mechanisms of psoriasis by comparing immunoreactivity of various chemokines and chemokine receptors between lesional and non-lesional skin of psoriasis. METHODS:We have performed immunohistochemical studies with mouse anti-human IL-8, mouse anti-human GRO, anti-huamn MCP-1, mouse anti-human RANTES, anti-human CDw 128 IL-8RA/ CXCR1, and anti-human IL-8RB/CXCR2 for lesional and non-lesional skin of ten psoriatic patients. RESULTS: 1.Immunohistochemical reactivity for IL-8 is stronger in lesional epidermis than non-lesional epidermis(p<0.05) and immunohistochemical reactivity for GRO-alpha is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 2.Immunohistochemical reactivity for MCP-1 is stronger in lesional epidermis than non-lesional epidermis(p<0.05), and immunohistochemical reactivity for RANTES is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 3.Immunohistochemical reactivity for CXCR1 is stronger in lesional epidermis than non-lesional epidermis(p<0.05) and immunohistochemical reactivity for CXCR2 is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 4.Immunofluorescent staining reveals positive finding in epidermis of lesional psoriasis, but negative finding in CXCR2. CONCLUSION: These results suggest that psoriatic keratinocytes express CXC chemokines like IL-8 and GRO-alpha, and CC chemokines like MCP-1 and RANTES, which have a significant role in the accumulation of inflammatory cells in psoriatic skin and that both CXCR1 and CXCR2 receptors are also expressed in psoriatic keratinocytes, which suggests that IL-8 and GRO-alpha could have a role in the characteristic epidermal changes through binding to their receptors in psoriatic keratinocytes.
Animals ; Chemokine CCL5 ; Chemokines* ; Chemokines, CC ; Chemokines, CXC ; Epidermis ; Humans ; Interleukin-8 ; Keratinocytes ; Mice ; Psoriasis* ; Receptors, Chemokine* ; Receptors, Interleukin-8B ; Skin

BACKGROUND: Chemokines are molecules with chemotatic activities on selective leukocyte populations and are sub-grouped into alpha-chemokine acting primarily on PMNL (polymorphonuclear leukocyte) and beta-chemokines attracting mainly lymphocytes and monocytes. We conducted a prospective study to investigate the serum levels of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1 alpha in patients with acute ischemic stroke and carotid atherosclerosis. METHODS: Serum was sampled from patients with acute ischemic stroke (<24hrs), with persistent ischemic neurological deficits associated with atherosclerosis (>1 month), and from normal subjects without a history of vascular disease. Concentrations of chemokines were measured by enzyme linked immunosorbent assay ( ELISA ). RESULTS: Compared with carotid atherosclerotic patients and control subjects, the serum levels of IL-8 were significantly elevated in those with acute ischemic stroke. The serum levels of MCP-1 in patients with large artery disease were higher than those in patients with small vessel disease and cardioembolism. CONCLUSIONS: This study suggested that IL-8 can be involved in acute ischemic stroke and MCP-1 plays a role in the pathogenesis of atherosclerosis.
Arteries ; Atherosclerosis* ; Carotid Artery Diseases ; Chemokine CCL2* ; Chemokines ; Chemokines, CC ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-8* ; Interleukins ; Leukocytes ; Lymphocytes ; Macrophage Inflammatory Proteins* ; Macrophages* ; Monocytes* ; Prospective Studies ; Stroke* ; Vascular Diseases

BACKGROUND AND OBJECTIVES: The number of eosinophil in nasal polyps has been reported to be strongly elevated when compared to non-affected nasal tissue, indicating an important role for eosinophils in the pathogenesis of nasal polyposis. The mechanisms determining selective eosinophilic tissue infiltration into diseased nasal mucosa as yet are specualtive. Panleukotactic factors also known to be present on nasal polyps cannot explain the type-selective tissue infiltration in eosinophilic or neutrophilic-featured diseases. Chemokines are known to have leukocyte subtype-selective chemotactic properties in vitro and thus are candidates explaining leukocytic characteristic tissue infiltration. The aim of this study was to investigate whether specific chemokines are associated with different forms of nasal polyps. This study was designed to demonstrate the expressions of various CC chemokines. MATERIALS AND METHODS: Nasal polyp from patients with systemic allergy (AP group, n=7) and negative allergic skin tests (NP group, n=10) were sampled. Expressions of RANTES, eotaxin, MCP-1, MIP-1alpha,beta were studies by RT-PCR and immunohistochemical studies. RESULTS: Expression and mean density of RANTES, MCP-1, MIP-1beta were significantly stronger in NP group than in AP group (p<0.05). However, those of eotaxin and MIP-1alpha were significantly stronger in AP group than in NP group (p<0.01). CONCLUSION: This results suggest that only selective chemokines could be involved to develop the pathologic conditions in different type of nasal polyp.
Chemokine CCL3 ; Chemokine CCL4 ; Chemokine CCL5 ; Chemokines ; Chemokines, CC* ; Eosinophils ; Humans ; Hypersensitivity ; Leukocytes ; Nasal Mucosa ; Nasal Polyps* ; Skin Tests

BACKGROUNDType 1 diabetes has been recognized as an organ specific autoimmune disease owing to the immune destruction of pancreatic islet beta cells in genetically susceptible individuals. In both human and rodent models of type 1 diabetes, such as nonobese diabetic (NOD) mice, biobreeding rats, the disease has a distinct stage characterized by immune cells infiltrating in the pancreas (insulitis). The major populations of infiltrating cells are macrophages and T lymphocytes. Therefore, immune cell infiltration of pancreatic islets may be a crucial step in the pathogenesis of type 1 diabetes. Monocyte chemoattractant protein-1 can specifically attract monocytes in vivo. Interferon induced protein-10 has chemoattractant effects on the activated lymphocytes. In this study, we analysed the expression of monocyte chemoattractant protein-1 in the pancreas of mice and interferon inducible protein-10 mRNA in the pancreas of NOD mice, and discussed their possible role in the pathogenesis of type 1 diabetes.

METHODSThe immunohistochemical method and immunoelectronmicroscopy were used to evaluate the expression of monocyte chemoattractant protein-1 in the pancreas of NOD mice and BALB/c mice. RT-PCR was used to evaluate the expression of monocyte chemoattractant protein-1 and interferon inducible protein mRNA in NOD mice.

RESULTSMonocyte chemoattractant protein-1 was positive in the pancreas of NOD mice, whereas negative in the pancreas of BALB/C mice. RT-PCR showed that monocyte chemoattractant protein-1 and interferon inducible protein-10 mRNA could be found in the pancreas of NOD mice. Immunoelectronmicroscopy demonstrated that monocyte chemoattractant protein-1 was produced by beta cells and stored in the cytoplasm of the cells.

CONCLUSIONSPancreatic islet beta cells produce monocyte chemoattractantprotein-1 in NOD mice. Monocyte chemoattractant protein-1 may play an important part in the pathogenesis of type 1 diabetes by attracting monocytes/macrophages to infiltrate pancreatic islets.

Animals ; Chemokine CCL2 ; analysis ; genetics ; Chemokine CXCL10 ; Chemokines, CXC ; genetics ; Diabetes Mellitus, Type 1 ; etiology ; metabolism ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Microscopy, Immunoelectron ; Pancreas ; chemistry ; RNA, Messenger ; analysis

OBJECTIVETo study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment.

METHODSTwelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed.

RESULTSAlthough steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN.

CONCLUSIONSThe efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.

Adolescent ; Adrenal Cortex Hormones ; administration & dosage ; Adult ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Biopsy ; Chemokine CCL2 ; analysis ; Chemokine CCL3 ; Chemokine CCL4 ; Chemokines, CC ; analysis ; Child ; Cyclophosphamide ; administration & dosage ; Female ; Glomerulonephritis ; drug therapy ; immunology ; pathology ; Humans ; Kidney Glomerulus ; chemistry ; pathology ; Macrophage Inflammatory Proteins ; analysis ; Male ; Middle Aged

PURPOSE: To better understand the extent to which chemokines participate in the mucosal inflammatory response in patients with ulcerative colitis (UC), we assessed the expression of an array of chemokines in the colonic mucosa of UC patients. METHODS: Colonic mucosal biopsy specimens were obtained from 15 patients with UC and 12 normal controls. Messenger RNA (mRNA) levels for 10 chemokines were quantitated by reverse-transcription PCR using synthetic standard RNAs. The biopsy specimens were also cultured, and secreted chemokines in culture supernatants were assayed by ELISA. RESULTS: The mRNA expression of C-X-C (IL-8, GROalpha, GRObeta, GROgamma, ENA-78, and IP-10) and C-C (MCP-1, MIP-1beta, and RANTES), but not C (lymphotactin) chemokines was significantly higher in the affected mucosa of UC patients than in the unaffected mucosa of UC patients or in the normal mucosa of normal controls. The degree of increased expression was more prominent in the C-X-C than in the C-C chemokines. Further, the secretion of IL-8, GROalpha, ENA-78, and MCP-1 was higher in UC patients than in normal controls. Secretions of MIP-1beta and RANTES also showed a trend toward an increase in UC, but it did not reach statistical significance. CONCLUSION: The increased expression of a variety of chemokines in UC suggest that chemokines may play an important role in the immunopathogenesis of UC.
Biopsy ; Chemokine CCL4 ; Chemokine CCL5 ; Chemokines* ; Chemokines, CC ; Colitis, Ulcerative* ; Colon* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-8 ; Mucous Membrane* ; Polymerase Chain Reaction ; RNA ; RNA, Messenger ; Ulcer*

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) belongs to C-C subfamily of chemokines, which stimulates the migration of monocytes. MCP-1 exerts various effects on the monocytes, including the induction of integrin and tissue factor, and synthesis of proinflammatory cytokines and arachidonic acid. In this study, we measured the MCP-1 levels in patients with Behcet's disease and evaluated the associations between the levels of MCP-1 and the level of other chemokines and various clinical features of Behcet's disease. METHODS: Serum samples were obtained from 67 patients with Behcet's disease and 30 healthy controls. Simultaneously, whole blood was isolated from patients (n=25) with Behcet's disease and healthy controls (n=11) and cultured in 24 well plates for 48 hours in the absence or presence of lipopolysaccharide (LPS) 5 microgram/mL, phytohaemagglutinin (PHA) 5 microgram/mL, phorbol 12-myristate 13-acetate (PMA) 50 ng/mL + ionomycin 5 microgram/mL. The MCP-1 concentrations were measured in the sera and culture supernatants by enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of serum MCP-1 were 2.5 times higher in patients with Behcet's disease than healthy controls. The patients with Behcet's disease had also higher levels of MCP-1 in the culture supernatants of whole blood cells, stimulated with LPS, but not with either PHA or PMA plus ionomycin, compared to healthy controls. Serum MCP-1 levels (n=67) were strongly correlated with serum RANTES, MIP-1alpha, IL-8 levels in Behcet's disease. In addition, the production of MCP-1 by whole blood culture from Behcet's disease patients (n=25) were also correlated well with those of RANTES, MIP-1alpha, and IL-8, when stimulated with LPS. However, MCP-1 levels in the sera and culture supernatants did not show any association with various clinical features of Behcet's disease including oral ulcer, genital ulcer, erythema nodosum, arthritis, uveitis, intestinal involvement, central nervous system involvement, and vascular thrombosis. CONCLUSION: In the sera and culture supernatants of whole blood stimulated with LPS, MCP-1 levels were higher in patients with Behcet's disease than controls and correlated well with RANTES, MIP-1alpha, IL-8 levels. These results suggest that the activation and migration of monocytes triggered by the increased production of MCP-1 may play a role in the pathogenesis of Behcet's disease.
Arachidonic Acid ; Arthritis ; Blood Cells ; Central Nervous System ; Chemokine CCL2* ; Chemokine CCL3 ; Chemokine CCL5 ; Chemokines ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Erythema Nodosum ; Humans ; Interleukin-8 ; Ionomycin ; Monocytes* ; Oral Ulcer ; Thromboplastin ; Thrombosis ; Ulcer ; Uveitis

BACKGROUND AND OBJECTIVES: The cause of nasal polyp is unsure but inflammation is thought to be an important factor in the development of nasal poyps. CC chemokine is a powerful chemotactic cytokine for inflammatory cells. We designed this study to investigate whether specific CC chemokines are associated with different forms of nasal polyps and their changes according to antibiotic treatment. MATERIALS AND METHODS: Nasal polyp from patients with atopy (AP group, n=12) and without atopy (NP group, n=20) were sampled. Expressions of RANTES, eotaxin, MCP-2, MCP-3 and MIP-1alpha were studied by an immunohistochemical study. Specimens of non-allergic nasal turbinates were used as the control group from 14 patients who were operated for nasal blockage. All patients were divided into 2 groups. One group was treated with antibiotics for 10 days before operation. The other was non-treated. RESULTS: Between the NP and AP group, the ratio of stained cells except anti-MCP 2 monoclonal antibody in the AP group was more increased than that of the NP group. Among them, RANTES and eotaxin were increased significantly (p<0.05). There was a significant difference of the expression of 5 CC chemokines between the treated and non-treated groups (p<0.05). CONCLUSIONS: These results suggest that chemokines play an important role in the development of nasal polyps, and different kinds of chemokines can be involved according to the cause of nasal polyps and CC chemokines affected by antibiotic treatment.
Anti-Bacterial Agents ; Chemokine CCL3 ; Chemokine CCL5 ; Chemokines ; Chemokines, CC ; Humans ; Inflammation ; Nasal Obstruction ; Nasal Polyps* ; Turbinates