Role of the Host Inflammatory Response in Colon Carcinoma Initiation, Progression and Liver Metastasis

2010 ◽  
pp. 289-319 ◽  
Author(s):  
Pnina Brodt
Keyword(s):  
Liver Metastasis ◽  
Inflammatory Response ◽  
Colon Carcinoma ◽  
Host Inflammatory Response

scholarly journals Giardia duodenalis Induces Proinflammatory Cytokine Production in Mouse Macrophages via TLR9-Mediated p38 and ERK Signaling Pathways

2021 ◽  
Vol 9 ◽  
Author(s):  
Xudong Pu ◽  
Xin Li ◽  
Lili Cao ◽  
Kaiming Yue ◽  
Panpan Zhao ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Proinflammatory Cytokines ◽  
Giardia Duodenalis ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Mouse Macrophages ◽  
Host Inflammatory Response

Giardia duodenalis, also known as Giardia lamblia or Giardia intestinalis, is an important opportunistic, pathogenic, zoonotic, protozoan parasite that infects the small intestines of humans and animals, causing giardiasis. Several studies have demonstrated that innate immunity-associated Toll-like receptors (TLRs) are critical for the elimination of G. duodenalis; however, whether TLR9 has a role in innate immune responses against Giardia infection remains unknown. In the present study, various methods, including reverse transcriptase–quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, immunofluorescence, inhibitor assays, and small-interfering RNA interference, were utilized to probe the role of TLR9 in mouse macrophage-mediated defenses against G. lamblia virus (GLV)–free or GLV-containing Giardia trophozoites. The results revealed that in G. duodenalis–stimulated mouse macrophages, the secretion of proinflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-12 p40, was enhanced, concomitant with the significant activation of TLR9, whereas silencing TLR9 attenuated the host inflammatory response. Notably, the presence of GLV exacerbated the secretion of host proinflammatory cytokines. Moreover, G. duodenalis stimulation activated multiple signaling pathways, including the nuclear factor κB p65 (NF-κB p65), p38, ERK, and AKT pathways, the latter three in a TLR9-dependent manner. Additionally, inhibiting the p38 or ERK pathway downregulated the G. duodenalis–induced inflammatory response, whereas AKT inhibition aggravated this process. Taken together, these results indicated that G. duodenalis may induce the secretion of proinflammatory cytokines by activating the p38 and ERK signaling pathways in a TLR9-dependent manner in mouse macrophages. Our in vitro findings on the mechanism underlying the TLR9-mediated host inflammatory response may help establish the foundation for an in-depth investigation of the role of TLR9 in the pathogenicity of G. duodenalis.

scholarly journals 971. The Role of Inflammation and Innate Effectors in Passive Immunization for Acinetobacter baumannii Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S33-S33
Author(s):  
Travis B Nielsen ◽  
Jun Yan ◽  
Brian M Luna ◽  
Yuli Talyansky ◽  
Robert A Bonomo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Passive Immunization ◽  
Reciprocal Relationship ◽  
Bacterial Density ◽  
Therapeutic Approaches ◽  
Blood Isolate ◽  
Primary Driver ◽  
Innate Effector ◽  
Host Inflammatory Response

Abstract Background We have previously demonstrated that A. baumannii virulence is driven by avoidance of innate effector clearance, resulting in LPS-TLR4 triggering of excess inflammation in the host. We also raised a monoclonal antibody (MAb) that improved survival of mice lethally infected with A. baumannii. Methods Mice were selectively depleted of innate effectors (macrophages with liposomal clodronate, neutrophils with cyclophosphamide, and/or complement with cobra venom factor), infected with an XDR clinical blood isolate of A. baumannii, and treated with placebo or anti-A. baumannii MAb. Results Single disruption of macrophages or neutrophils did not enhance lethality but complement deficiency did. In contrast, singly disrupting complement or neutrophils did not impact bacterial density but macrophage disruption markedly increased it. Thus, a dissociation of bacterial density and survival was observed. MAb therapy was completely protective in mice depleted of a single effector. While dual depletion resulted in diminished MAb efficacy in terms of survival, mice retaining neutrophils had marked improvements in survival with MAb therapy compared with other dual-depletion groups. The dissociation of bacterial density and survival suggested that inflammation was a primary driver of host outcome. Levels of IL-10 and TNFα had a reciprocal relationship in mice across effector depletion groups and were lower in mouse groups with higher survival when adjusted for bacterial density. IL-10 disruption completely abrogated the survival benefit of MAb therapy without altering bacterial clearance mediated by MAb. In contrast, TNFα disruption enhanced MAb efficacy for survival, and the presence of TNFα was antagonistic to MAb efficacy. Conclusion These results confirm that host outcomes from A. baumannii infection are driven by host inflammatory response rather than bacterial density alone. Furthermore, novel therapeutic approaches seeking to improve outcomes from such infections must seek to shift the balance of pro-/anti-inflammatory cytokines to favor a down-modulated inflammatory response. Disclosures All Authors: No reported Disclosures.

COX-2 increases adhesion of human colon carcinoma cells—Possible role of NSAIDs in suppression of liver metastasis

2001 ◽  
Vol 120 (5) ◽  
pp. A595-A595
Author(s):  
Y KAKIUCHI ◽  
S TSUJI ◽  
M TSUJII ◽  
N KAWAI ◽  
M YASUMARU ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Colon Carcinoma ◽  
Human Colon ◽  
Carcinoma Cells ◽  
Colon Carcinoma Cells ◽  
Human Colon Carcinoma ◽  
Cox 2

COX-2 increases adhesion of human colon carcinoma cells—Possible role of NSAIDs in suppression of liver metastasis

2001 ◽  
Vol 120 (5) ◽  
pp. A595
Author(s):  
Yoshimi Kakiuchi ◽  
Shingo Tsuji ◽  
Masahiko Tsujii ◽  
Naoki Kawai ◽  
Masakazu Yasumaru ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Colon Carcinoma ◽  
Human Colon ◽  
Carcinoma Cells ◽  
Colon Carcinoma Cells ◽  
Human Colon Carcinoma ◽  
Cox 2

scholarly journals Implication of HisF fromAcinetobacter baumanniiin persistence during a pneumonia infection

2019 ◽  
Author(s):  
Marta Martínez-Guitián ◽  
Juan C. Vázquez-Ucha ◽  
Laura Álvarez-Fraga ◽  
Kelly Conde-Pérez ◽  
Juan A. Vallejo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mutant Strain ◽  
Inflammatory Cytokines ◽  
Negative Regulator ◽  
Host Inflammatory Response ◽  
Pro Inflammatory Cytokines

ABSTRACTThehisFgene fromA. baumanniiATCC 17978 was found over-expressed during a murine pneumonia infection. A mutant strain lackinghisFshowed its involvement in virulence during mice pneumonia as well as in host inflammatory response, where the product of HisF may act as negative regulator in the production of pro-inflammatory cytokines. This work evaluates the role of HisF in theA. baumanniipathogenesis and suggests its potential as a new target for antimicrobial therapies.

scholarly journals Role of Proapoptotic BAX in Propagation ofChlamydia muridarum(the Mouse Pneumonitis Strain ofChlamydia trachomatis) and the Host Inflammatory Response

2002 ◽  
Vol 278 (11) ◽  
pp. 9496-9502 ◽  
Author(s):  
Jean-Luc Perfettini ◽  
David M. Ojcius ◽  
Charles W. Andrews ◽  
Stanley J. Korsmeyer ◽  
Roger G. Rank ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Ofchlamydia Trachomatis ◽  
Host Inflammatory Response

Role of virulence factors on host inflammatory response induced by diarrheagenicEscherichia colipathotypes

2015 ◽  
Vol 10 (6) ◽  
pp. 1009-1033 ◽  
Author(s):  
Javier Sanchez-Villamil ◽  
Fernando Navarro-Garcia
Keyword(s):  
Inflammatory Response ◽  
Virulence Factors ◽  
Host Inflammatory Response

scholarly journals Fas Ligand Deficiency Impairs Host Inflammatory Response against Infection with the Spirochete Borrelia burgdorferi

2006 ◽  
Vol 74 (2) ◽  
pp. 1156-1160 ◽  
Author(s):  
Cuixia Shi ◽  
Julie Wolfe ◽  
Jennifer Q. Russell ◽  
Karen Fortner ◽  
Nicholas Hardin ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Borrelia Burgdorferi ◽  
Fas Ligand ◽  
Cell Types ◽  
Lyme Arthritis ◽  
Host Responses ◽  
Synovial Lining ◽  
Synovial Tissues ◽  
Host Inflammatory Response

ABSTRACT Lyme disease represents a complex response to Borrelia burgdorferi that involves both bacterial factors as well as host responses. This results in an inflammatory reaction at several sites, including the synovial lining of joints. Synovial tissues of inflamed joints contain cells expressing high levels of Fas and Fas ligand (FasL). Although Fas stimulation is typically associated with cell death, it can also transmit stimulatory signals to certain cell types. Among these are dendritic cells and macrophages, which are abundant in inflamed synovium. To better assess the role of FasL in the pathogenesis of Lyme arthritis, we evaluated the response to B. burgdorferi infection in C3H/HeJgld mice that bear a nonfunctional mutation in FasL. Compared to wild-type C3H+/+ mice, C3Hgld mice had a similar bacterial burden and antibody response 2 weeks and 4 weeks following infection, but they manifested a significantly reduced Borrelia-specific cytokine response. In addition, C3Hgld mice developed a greatly reduced incidence and severity of arthritis. The findings document a contribution of FasL to the host inflammatory response to B. burgdorferi.

scholarly journals The Host Inflammatory Response Promotes Liver Metastasis by Increasing Tumor Cell Arrest and Extravasation

2007 ◽  
Vol 170 (5) ◽  
pp. 1781-1792 ◽  
Author(s):  
Patrick Auguste ◽  
Lucia Fallavollita ◽  
Ni Wang ◽  
Julia Burnier ◽  
Andreas Bikfalvi ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Inflammatory Response ◽  
Tumor Cell ◽  
Cell Arrest ◽  
Host Inflammatory Response

scholarly journals Targeting the complement system in bacterial meningitis

Brain ◽  
2019 ◽  
Vol 142 (11) ◽  
pp. 3325-3337 ◽  
Author(s):  
Diederik L H Koelman ◽  
Matthijs C Brouwer ◽  
Diederik van de Beek
Keyword(s):  
Bacterial Meningitis ◽  
Inflammatory Response ◽  
Complement System ◽  
Morbidity And Mortality ◽  
Treatment Target ◽  
Anaphylatoxin C5a ◽  
Promising Treatment ◽  
The Complement System ◽  
Host Inflammatory Response

Morbidity and mortality in bacterial meningitis are driven by an uncontrolled host inflammatory response. Koelman et al. evaluate the detrimental role of the complement system in spurring this inflammation, and conclude that anaphylatoxin C5a is a promising treatment target in bacterial meningitis.

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