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Glycyrrhizin inhibits neutrophil-associated generation of alternatively activated macrophages
Tsuyoshi Yoshida1, Yasuhiro Tsuda, Dan Takeuchi
1Department of Internal Medicine, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0435, USA.
Abstract:
Patients with severe burn injuries are extremely susceptible to infection, and the host's antibacterial responses are frequently suppressed by alternatively activated macrophages (M2Mphi), commonly demonstrated in these patients. An immunosuppressive subset of neutrophils (PMN-II), demonstrated in the peripheral blood of thermally injured patients, has been described as an inducer of M2Mphi. In the present studies, the inhibitory effect of glycyrrhizin (GL) on M2Mphi generation stimulated by PMN-II was examined. M2Mphi were generated from resident Mphi (R-Mphi, lower chamber) after cultivation with PMN-II (upper chamber) in a dual-chamber transwell. However, M2Mphi were not generated from R-Mphi when the same transwell cultures were performed in the presence of GL. M2Mphi were not generated from R-Mphi after cultivation with PMN-II previously treated with GL, while R-Mphi previously treated with GL converted to M2Mphi after they were cultured with PMN-II in transwells. Interleukin-10 and CCL2 released from PMN-II were shown to be effector molecules responsible for the generation of M2Mphi. However, these soluble factors were not produced by PMN-II treated with GL. These results indicate that GL inhibits PMN-II-stimulated M2Mphi generation through the inhibition of CCL2/interleukin-10 production by PMN-II.
Insights
Glycyrrhizin (GL) inhibits the generation of immunosuppressive alternatively activated macrophages (M2Mphi) in burn patients. This compound blocks neutrophils (PMN-II) from producing key signaling molecules, thereby reducing infection susceptibility.
Area of Science:
- Immunology
- Wound Healing
- Pharmacology
Background:
- Severe burn injuries increase infection risk due to suppressed antibacterial responses.
- Alternatively activated macrophages (M2Mphi) and immunosuppressive neutrophils (PMN-II) are implicated in burn-induced immune suppression.
- PMN-II are known to induce M2Mphi generation.
Purpose of the Study:
- To investigate the inhibitory effect of glycyrrhizin (GL) on M2Mphi generation stimulated by PMN-II.
- To elucidate the mechanism by which GL affects PMN-II-induced M2Mphi production.
Main Methods:
- Dual-chamber transwell cultures were used to model M2Mphi generation from resident macrophages (R-Mphi) stimulated by PMN-II.
- The effect of GL was assessed by adding it to the cultures or pre-treating PMN-II or R-Mphi with GL.
- Levels of interleukin-10 and CCL2 produced by PMN-II were measured.
Main Results:
- GL significantly inhibited the generation of M2Mphi from R-Mphi when co-cultured with PMN-II.
- GL prevented M2Mphi generation even when PMN-II were pre-treated with GL.
- GL treatment of PMN-II abolished the production of interleukin-10 and CCL2, which are crucial for M2Mphi induction.
Conclusions:
- Glycyrrhizin effectively inhibits the generation of immunosuppressive M2Mphi induced by PMN-II in a burn injury context.
- GL acts by suppressing the production of interleukin-10 and CCL2 by PMN-II.
- These findings suggest GL as a potential therapeutic agent to restore immune function in burn patients.
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