Potential Role of the Chemokine Macrophage Inflammatory Protein 1α in Human and Experimental Schistosomiasis

ABSTRACT In human schistosomiasis, the concentrations of the chemokine macrophage inflammatory protein 1α (MIP-1α/CCL3) is greater in the plasma of patients with clinical hepatosplenic disease. The objective of the present study was to confirm the ability of CCL3 to detect severe disease in patients classified by ultrasonography (US) and to evaluate the potential role of CCL3 in Schistosoma mansoni-infected mice. CCL3 was measured by enzyme-linked immunosorbent assay in the plasma of S. mansoni-infected patients. CCL3-deficient mice were infected with 25 cercariae, and various inflammatory and infectious indices were evaluated. The concentration of CCL3 was higher in the plasma of S. mansoni-infected than noninfected patients. Moreover, CCL3 was greater in those with US-defined hepatosplenic than with the intestinal form of the disease. In CCL3-deficient mice, the size of the granuloma and the liver eosinophil peroxidase activity and collagen content were diminished compared to wild-type mice. In CCL3-deficient mice, the worm burden after 14 weeks of infection, but not after 9 weeks, was consistently smaller. The in vitro response of mesenteric lymph node cells to antigen stimulation was characterized by lower levels of interleukin-4 (IL-4) and IL-10. CCL3 is a marker of disease severity in infected humans, and experimental studies in mice suggest that CCL3 may be a causative factor in the development of severe schistosomiasis.

Download Full-text

Role of Macrophage Inflammatory Protein-1α in T-Cell-Mediated Immunity to Viral Infection

Journal of Virology ◽

10.1128/jvi.77.22.12378-12384.2003 ◽

2003 ◽

Vol 77 (22) ◽

pp. 12378-12384 ◽

Cited By ~ 8

Author(s):

Andreas N. Madsen ◽

Anneline Nansen ◽

Jan P. Christensen ◽

Allan R. Thomsen

Keyword(s):

T Cell ◽

Lymphocytic Choriomeningitis ◽

Lymphocytic Choriomeningitis Virus ◽

Effector T Cells ◽

Cell Mediated Immunity ◽

Inflammatory Protein ◽

Specific Effector ◽

Macrophage Inflammatory Protein ◽

Deficient Mice

ABSTRACT The immune response to lymphocytic choriomeningitis virus in mice lacking macrophage inflammatory protein-1α (MIP-1α) was evaluated. Generation of virus-specific effector T cells is unimpaired in MIP-1α-deficient mice. Furthermore, MIP-1α is not required for T-cell-mediated virus control or virus-induced T-cell-dependent inflammation. Thus, MIP-1α is not mandatory for T-cell-mediated antiviral immunity.

Download Full-text

Impaired Pulmonary NF-κB Activation in Response to Lipopolysaccharide in NADPH Oxidase-Deficient Mice

Infection and Immunity ◽

10.1128/iai.69.10.5991-5996.2001 ◽

2001 ◽

Vol 69 (10) ◽

pp. 5991-5996 ◽

Cited By ~ 62

Author(s):

M. Audrey Koay ◽

John W. Christman ◽

Brahm H. Segal ◽

Annapurna Venkatakrishnan ◽

Thomas R. Blackwell ◽

...

Keyword(s):

Nadph Oxidase ◽

Intracellular Signaling ◽

Lung Inflammation ◽

Nuclear Translocation ◽

Binding Activity ◽

Wild Type ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein ◽

Deficient Mice

ABSTRACT Reactive oxygen species (ROS) are thought to be involved in intracellular signaling, including activation of the transcription factor NF-κB. We investigated the role of NADPH oxidase in the NF-κB activation pathway by utilizing knockout mice (p47phox−/−) lacking the p47phox component of NADPH oxidase. Wild-type (WT) controls and p47phox−/−mice were treated with intraperitoneal (i.p.) Escherichia coli lipopolysaccharide (LPS) (5 or 20 μg/g of body weight). LPS-induced NF-κB binding activity and accumulation of RelA in nuclear protein extracts of lung tissue were markedly increased in WT compared to p47phox−/− mice 90 min after treatment with 20 but not 5 μg of i.p. LPS per g. In another model of lung inflammation, RelA nuclear translocation was reduced in p47phox−/− mice compared to WT mice following treatment with aerosolized LPS. In contrast to NF-κB activation in p47phox−/− mice, LPS-induced production of macrophage inflammatory protein 2 in the lungs and neutrophilic lung inflammation were not diminished in these mice compared to WT mice. We conclude that LPS-induced NF-κB activation is deficient in the lungs of p47phox−/− mice compared to WT mice, but this abnormality does not result in overt alteration in the acute inflammatory response.

Download Full-text

Stat5a/b contribute to interleukin 7–induced B-cell precursor expansion, but abl- andbcr/abl-induced transformation are independent of Stat5

Blood ◽

10.1182/blood.v96.6.2277 ◽

2000 ◽

Vol 96 (6) ◽

pp. 2277-2283 ◽

Cited By ~ 154

Author(s):

Veronika Sexl ◽

Roland Piekorz ◽

Richard Moriggl ◽

Juerg Rohrer ◽

Michael P. Brown ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Interleukin 4 ◽

Target Cells ◽

Interleukin 7 ◽

And Function ◽

Deficient Mice

Abstract The cytokines interleukin 7 (IL-7) and interleukin 4 (IL-4) regulate lymphoid differentiation and function and activate the transcription factor Stat5. Using mice deficient for the 2 highly related transcription factors, Stat5a and Stat5b (Stat5a/b−/−), we investigated the role of Stat5 for B-cell differentiation, expansion, and function. Peripheral blood B cells of Stat5-deficient mice are significantly reduced, but no proliferation defects in response to various mitogenic stimuli are found. Also, IgM and IgG1 antibody production and immunoglobulin class switching are not affected. Pre- and pro-B cells of Stat5-deficient animals were found to have reduced responses to IL-7. Pro- and pre-B cells are the target cells of the abloncogene and numerous studies have suggested that Stat5a/b is essential for transformation by derivatives of the Abelson(abl) gene. To assess the role of Stat5a/b in transformation, we have evaluated the ability of variousabl derivatives to transform cells from Stat5a/b-deficient mice in vitro or in vivo. We demonstrate that the absence of Stat5a/b is not essential for the induction of lymphoid or myeloid tumors in vivo or on the ability to transform bone marrow cells in vitro.

Download Full-text

Chemokines in the gastric mucosa in Helicobacter pylori infection

Gut ◽

10.1136/gut.42.5.609 ◽

1998 ◽

Vol 42 (5) ◽

pp. 609-617 ◽

Cited By ~ 138

Author(s):

Y Yamaoka ◽

M Kita ◽

T Kodama ◽

N Sawai ◽

T Tanahashi ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Expression Patterns ◽

Enzyme Linked Immunosorbent Assay ◽

Biopsy Specimens ◽

Inflammatory Protein ◽

Polymerase Chain ◽

H Pylori ◽

Macrophage Inflammatory Protein

Background—Although chemokines have been suggested to play an important role in Helicobacter pyloriassociated gastritis, few studies have investigated the role of chemokines other than interleukin 8 (IL-8) in gastric mucosa.Aims—To investigate the expression and production patterns of various chemokines using gastric biopsy specimens.Methods—In 192 patients, expression patterns of C-X-C chemokines (IL-8 and growth regulated α (GROα)) and C-C chemokines (regulated on activation, normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein 1α (MIP-1α), and MIP-1β) were examined using reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA).cagA gene was identified using PCR.Results—H pylori infection was associated with increased rates of expression of mRNA for IL-8, GROα, RANTES, and MIP-1α and with increased levels of mucosal IL-8 and GROα. IL-8 and GROα levels correlated with the density of H pylori in both the antrum and corpus. The levels of these chemokines correlated with cellular infiltration in the antrum but not the corpus. cagA gene positive H pyloriinfection was associated with increased rates of expression of mRNA for IL-8 and GROα and with increased levels of these chemokines.Conclusion—H pylori infection is associated with increased expression rates and production of C-X-C chemokines (IL-8 and GROα), but not with increased production of C-C chemokines. Although H pylori infection is associated with increased C-X-C chemokines in the antrum and corpus, there is a difference in the inflammatory response between these two areas of the stomach.

Download Full-text

Stem-cell treatment in disc degeneration: What is the evidence?

Coluna/Columna ◽

10.1590/s1808-18512013000100013 ◽

2013 ◽

Vol 12 (1) ◽

pp. 61-63

Author(s):

Manuela Peletti-Figueiró ◽

Pedro Guarise da Silva ◽

Olívia Egger de Souza ◽

Ana Paula Lambert ◽

Denise Cantarelli Machado ◽

...

Keyword(s):

Stem Cells ◽

Degenerative Disc Disease ◽

Clinical Studies ◽

Potential Role ◽

Experimental Studies ◽

Disc Disease ◽

Degenerative Disc ◽

Stem Cell Treatment

To review the potential role of stem cells in treating degenerative disc disease of the intervertebral disc (IVD). A review was performed of articles from the Medline database concerning stem cells and degenerative disc disease (DDD). To discuss the data, the papers were classified as: review, in vitro, experimental, and clinical. The currently available treatments were basically for symptom reduction, not to revert the IVD degenerative process. The use of mesenchymal stem cells (MSC) is being proposed as an option of treatment for DDD. In vitro studies have shown that the MSC are able to differentiate into NP cells and that the MSC also reduce the inflammatory levels of the degenerated IVD. Besides, experimental studies demonstrated that the MSC remained viable when injected into the IVD, and that they were able to regenerate partially from the degenerated IVD and its structure. The few clinical studies found in the literature presented diverging results. The use of MSC is being widely studied and shows promising results for the treatment of DDD. Although many advances are being achieved in studies in vitro and experimental, there is a lack of clinical studies to prove the role of MSC in DDD management.

Download Full-text

Macrophage Inflammatory Protein (MIP)-3α/CCL20 and Its Receptor CCR6 Are Overexpressed in the Bone Microenvironment and Involved in Osteoclast Formation in Multiple Myeloma Patients.

Blood ◽

10.1182/blood.v110.11.3510.3510 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3510-3510 ◽

Cited By ~ 1

Author(s):

Nicola Giuliani ◽

Gina Lisignoli ◽

Sara Tagliaferri ◽

Mirca Lazzaretti ◽

Francesca Morandi ◽

...

Keyword(s):

Multiple Myeloma ◽

Osteoclast Formation ◽

Bone Lesions ◽

Mrna Levels ◽

Bone Microenvironment ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein

Abstract Osteoclast (OC) activation in multiple myeloma (MM) is primarily due to the imbalance of the critical osteoclastogenic system RANKL/OPG in the bone microenvironment. Recent evidences indicate that chemokines, small chemoattractant proteins involved in cancer cell homing, may contribute to osteoclast formation and activation. However, whereas the role of the chemokine macrophage inflammatory protein (MIP)-1α in MM-induced OC activation is well established, the involvement of other chemokines is not known. In this study, we evaluated the potential role of MIP-3α/CCL20 and its receptor CCR6 in the pathophysiology of OC formation and osteolytic lesions in MM. First the effect of MIP-3α/CCL20 on in vitro osteoclast formation by peripheral monocytes was evaluated. (MIP)-3α/CCL20 significantly increased both the number of multinucleated TRAP+ OCs and RANK+ OC progenitor cells in presence of RANKL. In addition we found that (MIP)-3α/CCL20 increases RANKL mRNA levels in both human osteoblastic (OB) and bone marrow (BM) osteoprogenitor cells (preOB). Following, the potential production of (MIP)-3α/CCL20 by human MM cell lines (HMCLs) and fresh purified CD138+ MM cells was also checked. Significant levels of (MIP)-3α/CCL20 were detected in one out of nine HMCLs tested and in about 10% of purified MM cells by ELISA and immunohystochemistry. On the other hand we found that MM cells up-regulated (MIP)-3α/CCL20 secretion, in OB/PreOB cells and in OCs as well as its receptor CCR6 in OCs in co-culture systems in presence of a transwell insert. Among potential soluble factors involved in the up-regulation of MIP-3α/CCL20 by MM cells we found that IL-1β and TNFα together stimulate MIP-3α/CCL20 production in both OB and PreOB. The role of MIP-3α/CCL20 in OC activation by MM cells was finally demonstrated by finding that both blocking anti-(MIP)-3α/CCL20 and anti-CCR6 Abs. but not anti-IgG control significantly decreased OC formation induced by the conditioned medium of MM cells co-cultured with OB and OC, respectively. This chemokine system was further studied in vivo in MM patients. MIP-3α/CCL20 levels were detected in the BM plasma of MGUS subjects (n°=16) and in MM (n°=52) patients at the diagnosis in relationship with the presence of bone lesions (osteolytic n°= 32; non-osteolytic: n°=20). Significant higher MIP-3α/CCL20 levels were detected in MM patients vs. MGUS (mean ± SD: 51.9±2 vs. 21±3 pg/mL; p=0.01) and in MM osteolytic patients vs. non-osteolytic ones (mean ± SD: 70.8±5.9 vs. 13.8±1.1 pg/mL; p=0.001). Interestingly, no significant differences were observed between MGUS and non-osteolytic MM patients. By immunohystochemistry performed on BM biopsies, we consistently found that MIP-3α/CCL20 was over-expressed in OBs in osteolytic MM patients as compared to non-osteolytic ones. In addition we found that OCs showed a strong CCR6 staining in the areas with an increased number of OCs. In conclusion our data indicate that (MIP)-3α/CCL20 its receptor CCR6 are up-regulated in bone microenvironment by MM cells and involved in osteoclast formation and bone lesions in MM patients.

Download Full-text

Prevalence, Antigenic Specificity, and Bactericidal Activity of Poultry Anti-Campylobacter Maternal Antibodies

Applied and Environmental Microbiology ◽

10.1128/aem.67.9.3951-3957.2001 ◽

2001 ◽

Vol 67 (9) ◽

pp. 3951-3957 ◽

Cited By ~ 82

Author(s):

Orhan Sahin ◽

Qijing Zhang ◽

Jerrel C. Meitzler ◽

Brian S. Harr ◽

Teresa Y. Morishita ◽

...

Keyword(s):

Broiler Chickens ◽

Potential Role ◽

Maternal Antibodies ◽

Antigenic Specificity ◽

Enzyme Linked Immunosorbent Assay ◽

Poultry Production ◽

Serum Samples ◽

Animal Reservoir

ABSTRACT Poultry are considered the major reservoir for Campylobacter jejuni, a leading bacterial cause of human food-borne diarrhea. To understand the ecology of C. jejuni and develop strategies to control C. jejuni infection in the animal reservoir, we initiated studies to examine the potential role of anti-Campylobacter maternal antibodies in protecting young broiler chickens from infection by C. jejuni. Using an enzyme-linked immunosorbent assay (ELISA), the prevalence of anti-C. jejuni antibodies in breeder chickens, egg yolks, and broilers from multiple flocks of different farms were examined. High levels of antibodies to the organism were detected in serum samples of breeder chickens and in egg yolk contents. To determine the dynamics of anti-Campylobacter maternal antibody transferred from yolks to hatchlings, serum samples collected from five broiler flocks at weekly intervals from 1 to 28 or 42 days of age were also examined by ELISA. Sera from the 1-day and 7-day-old chicks showed high titers of antibodies to C. jejuni. Thereafter, antibody titers decreased substantially and were not detected during the third and fourth weeks of age. The disappearance of anti-Campylobacter maternal antibodies during 3 to 4 weeks of age coincides with the appearance of C. jejuniinfections observed in many broiler chicken flocks. As shown by immunoblotting, the maternally derived antibodies recognized multiple membrane proteins of C. jejuni ranging from 19 to 107 kDa. Moreover, in vitro serum bactericidal assays showed that anti-Campylobacter maternal antibodies were active in antibody-dependent complement-mediated killing of C. jejuni. Together, these results highlight the widespread presence of functional anti-Campylobacter antibodies in the poultry production system and provide a strong rationale for further investigation of the potential role of anti-C. jejunimaternal antibodies in protecting young chickens from infection byC. jejuni.

Download Full-text

Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.553911 ◽

2021 ◽

Vol 12 ◽

Author(s):

Madhu Shankar ◽

Nathalie Uwamahoro ◽

Emelie Backman ◽

Sandra Holmberg ◽

Maria Joanna Niemiec ◽

...

Keyword(s):

Tissue Damage ◽

Severe Disease ◽

Critical Role ◽

Wild Type ◽

Surgical Intensive Care ◽

Fungal Peritonitis ◽

Inflammatory Protein ◽

Intra Abdominal Infection ◽

Deficient Mice

Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease.

Download Full-text

Role of Gamma Interferon in the Pathogenesis of Severe Schistosomiasis in Interleukin-4-Deficient Mice

Infection and Immunity ◽

10.1128/iai.69.12.7445-7452.2001 ◽

2001 ◽

Vol 69 (12) ◽

pp. 7445-7452 ◽

Cited By ~ 16

Author(s):

Anne Camille La Flamme ◽

Elisabeth A. Patton ◽

Edward J. Pearce

Keyword(s):

Severe Disease ◽

Gamma Interferon ◽

Interleukin 4 ◽

No Production ◽

Wild Type ◽

Fatal Disease ◽

Ifn Γ ◽

Deficient Mice

ABSTRACT In the absence of interleukin-4 (IL-4), infection withSchistosoma mansoni leads to a severe fatal disease rather than the chronic survivable condition that occurs in wild-type (WT) mice. Because the sustained production of NO most closely correlates to weight loss and fatality in infected IL-4−/− mice and because gamma interferon (IFN-γ) is an important inducer of inducible NO synthase, infected IL-4−/− mice were treated with anti-IFN-γ antibodies to determine the role of IFN-γ during schistosomiasis in WT and IL-4−/− animals. When IFN-γ was neutralized, Th2 responses were enhanced and NO production was reduced in both WT and IL-4−/− mice. The decreased NO production correlated with a rescue of proliferation in splenocytes from infected IL-4−/− mice. Furthermore, the neutralization of IFN-γ in vivo improved the gross appearance of the liver and led to a reduction in granuloma size in infected IL-4−/− but not WT mice. However, the neutralization of IFN-γ in vivo did not affect the development of severe disease in infected IL-4−/− mice. These results suggest that while the increased production of IFN-γ does lead to some of the pathology observed in infected IL-4−/− mice, it is not ultimately responsible for cachexia and death.

Download Full-text

Stat5a/b contribute to interleukin 7–induced B-cell precursor expansion, but abl- andbcr/abl-induced transformation are independent of Stat5

Blood ◽

10.1182/blood.v96.6.2277.h8002277_2277_2283 ◽

2000 ◽

Vol 96 (6) ◽

pp. 2277-2283 ◽

Cited By ~ 10

Author(s):

Veronika Sexl ◽

Roland Piekorz ◽

Richard Moriggl ◽

Juerg Rohrer ◽

Michael P. Brown ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Interleukin 4 ◽

Target Cells ◽

Interleukin 7 ◽

And Function ◽

Deficient Mice

The cytokines interleukin 7 (IL-7) and interleukin 4 (IL-4) regulate lymphoid differentiation and function and activate the transcription factor Stat5. Using mice deficient for the 2 highly related transcription factors, Stat5a and Stat5b (Stat5a/b−/−), we investigated the role of Stat5 for B-cell differentiation, expansion, and function. Peripheral blood B cells of Stat5-deficient mice are significantly reduced, but no proliferation defects in response to various mitogenic stimuli are found. Also, IgM and IgG1 antibody production and immunoglobulin class switching are not affected. Pre- and pro-B cells of Stat5-deficient animals were found to have reduced responses to IL-7. Pro- and pre-B cells are the target cells of the abloncogene and numerous studies have suggested that Stat5a/b is essential for transformation by derivatives of the Abelson(abl) gene. To assess the role of Stat5a/b in transformation, we have evaluated the ability of variousabl derivatives to transform cells from Stat5a/b-deficient mice in vitro or in vivo. We demonstrate that the absence of Stat5a/b is not essential for the induction of lymphoid or myeloid tumors in vivo or on the ability to transform bone marrow cells in vitro.

Download Full-text