Publications by authors named "Quentin N Myrvik"
Article Synopsis
- The study investigates how cyclooxygenase-2 (COX-2) in alveolar macrophages responds to heat-killed Mycobacterium bovis BCG, focusing on its role in down-regulating inflammation.
- After exposure to the bacteria, alveolar macrophages primarily express inactive, NE-dissociated COX-2 and do not release prostaglandin E(2) (PGE(2)), which suggests a suppression of inflammatory response despite the presence of COX-2.
- In contrast to peritoneal macrophages, which clear the bacteria quickly, alveolar macrophages retain the COX-2 enzyme and bacteria for an extended period, indicating sustained mycobacterial presence and altered inflammatory signaling.
Article Synopsis
- Macrophages activate rapidly when they ingest chitin microparticles, triggering MAPK pathways and releasing Th1 cytokines, excluding IL-10.
- The study found that depleting membrane cholesterol using methyl-beta-cytodextrin (MBCD) didn’t affect chitin’s binding or phagocytosis but increased MAPK phosphorylation and production of TNF-alpha and COX-2.
- In contrast, responses to other bacterial components like CpG-ODN and HK-BCG were less affected by MBCD, highlighting that cholesterol in membrane structures significantly impacts macrophage activation by chitin.
Over 25 years ago, it was observed that peritoneal macrophages (Mphi) isolated from mice given heat-killed Mycobacterium bovis bacillus Calmette-Guérin (HK-BCG) i.p. did not release PGE(2).
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- Human intelectin-1 (hITLN-1) is a lectin that binds to galactofuranosyl residues found in microbial cell walls, differing significantly in structure and saccharide-binding specificity from mouse intelectin-1 (mITLN-1).
- Despite having high amino acid identity, hITLN-1 forms a trimer and is glycosylated, while mITLN-1 exists as an unglycosylated monomer.
- Binding studies indicate that hITLN-1 and mITLN-1 target different saccharides, showcasing their distinct biochemical properties despite their shared recognition of galactofuranosyl residues.
Article Synopsis
- Cyclooxygenase-2 (COX-2) in macrophages plays a crucial role in regulating immune responses against intracellular bacteria, specifically affecting the microbiocidal functions of these immune cells.
- Administration of heat-killed Mycobacterium bovis (HK-BCG) leads to two phases of COX-2 expression: an initial rapid response characterized by a catalytically inactive form and a later phase with an active form associated with the nuclear envelope.
- The study highlights that during the early phase, macrophages effectively clear HK-BCG, while in the later phase, the COX-2 association with the nuclear envelope correlates with reduced bacterial uptake and increased PGE(2) production, which downregulates macroph
Although immunocompetent hosts develop protective type 1 helper T cell (Th1) responses in mycobacterial infections, seroepidemiologic studies show that patients with atherosclerosis commonly express high antibody titers against mycobacterial heat shock protein (HSP) 65 and may develop a nonprotective type 2 helper T cell (Th2) response and advanced disease. These studies were undertaken to define mycobacterial dose requirements and kinetics for development of antibodies to HSP65, the Th1 to Th2 shift of immune response, and calcified atherosclerotic lesion development in the apo E-/- mouse. Fourteen-week apo E-/- female mice were treated intraperitoneally (ip) with heat-killed M.
View Article and Find Full Text PDFPrevious studies have shown that prostaglandin E(2) (PGE(2)) release by splenic F4/80(+) cyclooxygenase (COX)-2(+) macrophages (MØ) isolated from mice, treated with mycobacterial components, plays a major role in the regulation of immune responses. However, splenic MØ, isolated from untreated mice and treated in vitro with lipopolysaccharide and interferon-gamma, express COX-1 and COX-2 within 1 day but release only minimal amounts of PGE(2) following elicitation with calcium ionophore A23187. For further characterization of in vivo requirements for development of PGE(2)-releasing MØ (PGE(2)-MØ), C57Bl/6 [wild-type (WT)], and interleukin (IL)-10-deficient (IL-10(-/-)) mice were treated intraperitoneally with heat-killed Mycobacterium bovis bacillus Calmette-Guerin (HK-BCG).
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- A Th1 adjuvant should stimulate Th1 cytokines (like IL-12, IL-18, and TNF-alpha) while avoiding the Th2 cytokine IL-10, which can suppress Th1 responses.
- The study observed that RAW 264.7 macrophage-like cells processed chitin particles and showed significant activation of MAPK pathways, leading to high TNF-alpha and COX-2 production along with PGE(2) release.
- Unlike other bacterial components that also triggered IL-10 release, chitin particles specifically did not induce IL-10, suggesting they could serve as a unique Th1 adjuvant by promoting a stronger Th1 response without the suppression typically caused by IL-10.
Article Synopsis
- Hosts exposed to low doses of mycobacteria develop Th1 immunity, while higher doses trigger a shift to Th2 immunity due to the influence of Prostaglandin E2 (PGE2).
- The study observed that macrophages in the spleen release PGE2 in a dose-dependent manner when treated with heat-killed Mycobacterium bovis BCG, influencing cytokine production and immune response markers.
- Mice given higher doses showed increased Th2-related antibodies and cytokines, suggesting that PGE2 and PGHS-2 are key mediators in the transition from Th1 to Th2 responses in the immune system.
Different populations of mononuclear phagocytes (MO) show considerable diversity of cellular function including prostaglandin E2 (PGE2) biosynthesis. Certain bacterial components enhance PGE2 biosynthesis differentially in selected populations of MO. Interleukin (IL)-10 is proposed to inhibit modulation of PGE2 biosynthesis by down-regulating prostaglandin G/H synthase-2 (PGHS-2) expression.
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