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Differing signal requirements for the activation of macrophages from C3H/HeJ and C3H/OuJ mice
1Department of Microbiology and Immunology, State University of New York, Health Science Center at Brooklyn 11203.
Abstract:
Endotoxin-associated protein (EP) from Salmonella typhi stimulated the release of prostaglandin E2 (PGE2), interleukin-1 (IL-1), and interferon (IFN) activity in macrophages from the lipopolysaccharide (LPS) responder C3H/OuJ mouse strain. However, only PGE2 and IL-1 were stimulated by EP in macrophages from the LPS nonresponder C3H/HeJ mouse strain. LPS stimulated the release of PGE2, IL-1 and IFN activity in C3H/OuJ macrophages, but not in C3H/HeJ macrophages. The protein kinase C (PKC) activator phorbol myristic acid (PMA) stimulated PGE2 production in both strains but not IL-1 production, suggesting that signalling pathways other than PKC may be involved in IL-1 production. The calcium ionophore ionomycin stimulated PGE2 production in C3H/OuJ but not C3H/HeJ macrophages, suggesting a defective calcium-related pathway in the C3H/HeJ macrophages as compared to the C3H/OuJ cells.
Insights
Endotoxin-associated protein (EP) from Salmonella typhi differentially affects macrophage cytokine release. EP stimulates prostaglandin E2 (PGE2) and interleukin-1 (IL-1) in both LPS responder and nonresponder mice, but interferon (IFN) only in responders.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Salmonella typhi endotoxin-associated protein (EP) is implicated in host immune responses.
- Lipopolysaccharide (LPS) is a key component of Gram-negative bacterial outer membranes, triggering immune responses.
- Macrophages play a central role in innate immunity, responding to microbial stimuli.
Purpose of the Study:
- To investigate the differential effects of Salmonella typhi EP on macrophage cytokine production in LPS responder and nonresponder mouse strains.
- To elucidate the signaling pathways involved in EP-induced cytokine release, including protein kinase C (PKC) and calcium-dependent pathways.
Main Methods:
- Primary macrophages were isolated from LPS responder (C3H/OuJ) and nonresponder (C3H/HeJ) mouse strains.
- Macrophages were stimulated with EP, LPS, phorbol myristic acid (PMA), and ionomycin.
- The release of prostaglandin E2 (PGE2), interleukin-1 (IL-1), and interferon (IFN) activity was measured.
Main Results:
- EP stimulated PGE2, IL-1, and IFN release in C3H/OuJ macrophages, but only PGE2 and IL-1 in C3H/HeJ macrophages.
- LPS stimulated PGE2, IL-1, and IFN in C3H/OuJ macrophages, but not in C3H/HeJ macrophages.
- PMA stimulated PGE2 but not IL-1 in both strains, while ionomycin stimulated PGE2 only in C3H/OuJ macrophages, suggesting defective calcium signaling in C3H/HeJ cells.
Conclusions:
- Salmonella typhi EP elicits distinct cytokine responses in macrophages based on LPS responsiveness.
- The results suggest that PKC-independent and calcium-dependent pathways are involved in IL-1 and PGE2 production, respectively.
- C3H/HeJ macrophages exhibit defects in calcium-related signaling pathways compared to C3H/OuJ macrophages.