scholarly journals Haemophilus influenzae Porin Contributes to Signaling of the Inflammatory Cascade in Rat Brain

2001 ◽  
Vol 69 (1) ◽  
pp. 221-227 ◽  
Author(s):  
Massimiliano Galdiero ◽  
Michele D'Amico ◽  
Fernanda Gorga ◽  
Clara Di Filippo ◽  
Marina D'Isanto ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Serum Proteins ◽  
Necrosis Factor Alpha ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Factor Alpha ◽  
Interleukin 1Α ◽  
Macrophage Inflammatory Protein ◽  
Brain Water ◽  
Necrosis Factor

ABSTRACT In the present study we observed that the Haemophilus influenzae type b (Hib) porin, among the different surface bacterial components, is involved in the pathophysiology of bacterial meningitis. This study demonstrates that inoculation of Hib porin into the fourth cerebral ventricle causes the simultaneous expression of interleukin-1α (IL-1α), tumor necrosis factor alpha (TNF-α), and macrophage inflammatory protein 2 (MIP-2) at 6 h after inoculation. At 24 h, the expression of MIP-2 decreases while the expression of IL-1α and TNF-α increases. The mRNA expression of IL-1α, TNF-α, and MIP-2 is correlated with injury to the blood-brain barrier as demonstrated by the appearance of serum proteins and leukocytes in cerebrospinal fluid and by the increase in brain water content.

scholarly journals CCL20/Macrophage Inflammatory Protein 3α and Tumor Necrosis Factor Alpha Production by Primary Uterine Epithelial Cells in Response to Treatment with Lipopolysaccharide or Pam3Cys

2005 ◽  
Vol 73 (1) ◽  
pp. 476-484 ◽  
Author(s):  
Mardi A. Crane-Godreau ◽  
Charles R. Wira
Keyword(s):  
Tumor Necrosis Factor ◽  
Epithelial Cells ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Factor Alpha ◽  
Macrophage Inflammatory Protein ◽  
Necrosis Factor

ABSTRACT Having previously shown that CCL20/macrophage inflammatory protein 3α and tumor necrosis factor alpha (TNF-α) are released by polarized primary rat uterine epithelial cells (UEC) in response to Escherichia coli but not to Lactobacillus rhamnosus, we sought to determine if epithelial cells are responsive to pathogen-associated molecular patterns (PAMP), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), and Pam3Cys, a bacterial lipoprotein analog. Epithelial cells were grown to confluence on Nunc cell culture inserts prior to apical treatment with PAMPs. In response to LPS, LTA, and Pam3Cys (EMC Microcollection GmbH, Tübingen, Germany), CCL20 levels increased (4- to 10-fold) while PAMPs caused increased TNF-α (1- to 4-fold) in the medium collected after 24 h of incubation. Both apical and basolateral secretion of CCL20 and TNF-α increased in response to PAMPs, but treatments had no effect on cell viability and integrity, as measured by transepithelial resistance. Time course studies of CCL20 and TNF-α release in response to Pam3Cys and LPS indicated that CCL20 release peaked between 2 and 4 h after treatment, whereas TNF-α release was gradual over the length of the incubation. Freeze-thaw and cell lysis experiments, along with actinomycin D studies, suggested that CCL20 and TNF-α are synthesized in response to PAMP stimulation. Taken together, these studies demonstrate that E. coli and selected PAMPs have direct effects on the production of CCL20 and TNF-α without affecting cell integrity. Since CCL20 is known to be both chemotactic and antimicrobial, the increase in apical and basolateral release by UEC in response to PAMPs suggests a new mechanism of innate immune protection in the female reproductive tract.

scholarly journals Effects of Estradiol on Lipopolysaccharide and Pam3Cys Stimulation of CCL20/Macrophage Inflammatory Protein 3 Alpha and Tumor Necrosis Factor Alpha Production by Uterine Epithelial Cells in Culture

2005 ◽  
Vol 73 (7) ◽  
pp. 4231-4237 ◽  
Author(s):  
Mardi A. Crane-Godreau ◽  
Charles R. Wira
Keyword(s):  
Tumor Necrosis Factor ◽  
Epithelial Cells ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Ici 182,780 ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Factor Alpha ◽  
Macrophage Inflammatory Protein ◽  
Necrosis Factor

ABSTRACT We have previously demonstrated that rat uterine epithelial cells (UEC) produce CCL20/macrophage inflammatory protein 3 alpha (MIP3α) and tumor necrosis factor alpha (TNF-α) in response to live and heat-killed Escherichia coli and to the pathogen-associated molecular patterns (PAMP) lipopolysaccharide (LPS) and Pam3Cys. To determine whether estradiol (E2) modulates PAMP-induced CCL20/MIP3α and TNF-α secretion, primary cultures of rat UEC were incubated with E2 for 24 h and then treated with LPS or Pam3Cys or not treated for an additional 12 h. E2 inhibited the constitutive secretion of TNF-α and CCL20/MIP3α into culture media. Interestingly, E2 pretreatment enhanced CCL20/MIP3α secretion due to LPS and Pam3Cys administration. In contrast, and at the same time, E2 lowered the TNF-α response to both PAMP. To determine whether estrogen receptors (ER) mediated the effects of E2, epithelial cells were incubated with E2 and/or ICI 182,780, a known ER antagonist. ICI 182,780 had no effect on E2 inhibition of constitutive TNF-α and CCL20/MIP3α secretion. In contrast, ICI 182,780 reversed the stimulatory effect of E2 on LPS- and/or Pam3Cys-induced CCL20/MIP3α secretion as well as partially reversed the inhibitory effect of E2 on TNF-α production by epithelial cells. Overall, these results indicate that E2 regulates the production of TNF-α and CCL20/MIP3α by UEC in the absence as well as presence of PAMP. Since CCL20/MIP3α has antimicrobial activity and is chemotactic for immune cells, these studies suggest that regulation of CCL20/MIP3α and TNF-α by E2 and PAMP may have profound effects on innate and adaptive immune responses to microbial challenge in the female reproductive tract.

scholarly journals Limited Role for Interleukin-18 in the Host Protection Response to Pulmonary Infection with Pseudomonas aeruginosa in Mice

2004 ◽  
Vol 72 (10) ◽  
pp. 6176-6180 ◽  
Author(s):  
Chikara Nakasone ◽  
Kazuyoshi Kawakami ◽  
Tomoaki Hoshino ◽  
Yusuke Kawase ◽  
Koichi Yokota ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pulmonary Infection ◽  
Interleukin 18 ◽  
Necrosis Factor Alpha ◽  
Host Protection ◽  
Limited Role ◽  
Inflammatory Protein ◽  
Factor Alpha ◽  
Macrophage Inflammatory Protein ◽  
Necrosis Factor

ABSTRACT We report that clearance of Pseudomonas aeruginosa, accumulation of neutrophils, and synthesis of tumor necrosis factor alpha and macrophage inflammatory protein 2 in the infected lung were not largely different in interleukin-18 (IL-18) knockout or transgenic mice compared with control mice. Our results suggest a limited role for IL-18 in the host defense against P. aeruginosa.

scholarly journals Gene Expression and Production of Tumor Necrosis Factor Alpha, Interleukin-1β (IL-1β), IL-8, Macrophage Inflammatory Protein 1α (MIP-1α), MIP-1β, and Gamma Interferon-Inducible Protein 10 by Human Neutrophils Stimulated with Group B Meningococcal Outer Membrane Vesicles

2000 ◽  
Vol 68 (12) ◽  
pp. 6917-6923 ◽  
Author(s):  
José A. Lapinet ◽  
Patrizia Scapini ◽  
Federica Calzetti ◽  
Oliver Pérez ◽  
Marco A. Cassatella
Keyword(s):  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Necrosis Factor Alpha ◽  
Cytokines And Chemokines ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Inducible Protein ◽  
Necrosis Factor

ABSTRACT Accumulation of polymorphonuclear neutrophils (PMN) into the subarachnoidal space is one of the hallmarks of Neisseria meningitidis infection. In this study, we evaluated the ability of outer membrane vesicles (OMV) from N. meningitidis B to stimulate cytokine production by neutrophils. We found that PMN stimulated in vitro by OMV produce proinflammatory cytokines and chemokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-8, macrophage inflammatory protein 1α (MIP-1α), and MIP-1β. A considerable induction of gamma interferon (IFN-γ)-inducible protein 10 (IP-10) mRNA transcripts, as well as extracellular IP-10 release, was also observed when neutrophils were stimulated by OMV in combination with IFN-γ. Furthermore, PMN stimulated by OMV in the presence of IFN-γ demonstrated an enhanced capacity to release TNF-α, IL-1β, IL-8, and MIP-1β compared to stimulation with OMV alone. In line with its downregulatory effects on neutrophil-derived proinflammatory cytokines, IL-10 potently inhibited TNF-α, IL-1β, IL-8, and MIP-1β production triggered by OMV. Finally, a neutralizing anti-TNF-α monoclonal antibody (MAb) did not influence the release of IL-8 and MIP-1β induced by OMV, therefore excluding a role for endogenous TNF-α in mediating the induction of chemokine release by OMV. In contrast, the ability of lipopolysaccharide fromN. meningitidis B to induce the production of IL-8 and MIP-1β was significantly inhibited by anti-TNF-α MAb. Our results establish that, in response to OMV, neutrophils produce a proinflammatory profile of cytokines and chemokines which may not only play a role in the pathogenesis of meningitis but may also contribute to the development of protective immunity to serogroup B meningococci.

scholarly journals Suppression of Macrophage Activation with CNI-1493 Increases Survival in Infant Rats with Systemic Haemophilus influenzae Infection

2000 ◽  
Vol 68 (9) ◽  
pp. 5329-5334 ◽  
Author(s):  
Carl Granert ◽  
Hana Abdalla ◽  
Lars Lindquist ◽  
Asim Diab ◽  
Moiz Bakhiet ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Infant Rats ◽  
Cytokine Inhibition ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
The Brain ◽  
Necrosis Factor

ABSTRACT CNI-1493, a potent macrophage deactivator, was used to treat infant rats systemically infected with Haemophilus influenzae type b (Hib). CNI-1493 was injected 1 h prior to bacterial inoculation and 24 h later and resulted in a 75 percent increased rate of survival compared to that for untreated controls. The effect of CNI-1493 on the inflammatory response was studied by immunohistochemical detection of individual tumor necrosis factor alpha (TNF-α)-, interleukin 1 beta (IL-1β)-, and gamma interferon (IFN-γ)-producing cells in the spleen. A significant reduction of the incidence of TNF-α- and IL-1β-expressing cells was found for CNI-1493-treated animals. IFN-γ expression was not suppressed by CNI-1493, indicating that cytokine inhibition was specific in macrophages. CNI-1493 significantly reduced the number of infiltrating granulocytes in the brain from that for controls. This study provides evidence that CNI-1493 protects against lethal Hib infection by deactivating the inflammatory cascade in infant rats.

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