Host Intracellular Signaling Events and Pro-inflammatory Cytokine Production in African Trypanosomiasis

Abstract Acute kidney injury (AKI) is a complex syndrome with an abrupt decrease of kidney function, which is associated with high morbidity and mortality. Sepsis is the common cause of AKI. Mounting evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of sepsis-induced AKI. In this study, we aimed to illustrate the function and mechanism of lncRNA SNHG14 in lipopolysaccharide (LPS)-induced AKI. We found that SNHG14 was highly expressed in the plasma of sepsis patients with AKI. SNHG14 inhibited cell proliferation and autophagy and promoted cell apoptosis and inflammatory cytokine production in LPS-stimulated HK-2 cells. Functionally, SNHG14 acted as a competing endogenous RNA (ceRNA) to negatively regulate miR-495-3p expression in HK-2 cells. Furthermore, we identified that HIPK1 is a direct target of miR-495-3p in HK-2 cells. We also revealed that the SNHG14/miR-495-3p/HIPK1 interaction network regulated HK-2 cell proliferation, apoptosis, autophagy, and inflammatory cytokine production upon LPS stimulation. In addition, we demonstrated that the SNHG14/miR-495-3p/HIPK1 interaction network regulated the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) via modulating NF-κB/p65 signaling in LPS-challenged HK-2 cells. In conclusion, our findings suggested a novel therapeutic axis of SNHG14/miR-495-3p/HIPK1 to treat sepsis-induced AKI.

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Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses

Scientific Reports ◽

10.1038/s41598-020-79068-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ricardo Louzada da Silva ◽

Diana M. Elizondo ◽

Nailah Z. D. Brandy ◽

Naomi L. Haddock ◽

Thomas A. Boddie ◽

...

Keyword(s):

Immune Evasion ◽

Inflammatory Cytokine ◽

Leishmania Donovani ◽

Cytokine Production ◽

Inflammatory Responses ◽

Bone Marrow Cells ◽

Parasitic Infections ◽

Inflammatory Factor ◽

Immune Functions ◽

Inflammatory Cytokine Production

AbstractMacrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.

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Flutamide Attenuates Pro-inflammatory Cytokine Production and Hepatic Injury Following Trauma-Hemorrhage via Estrogen Receptor-related Pathway

Annals of Surgery ◽

10.1097/01.sla.0000232523.88621.17 ◽

2007 ◽

Vol 245 (2) ◽

pp. 297-304 ◽

Cited By ~ 42

Author(s):

Tomoharu Shimizu ◽

Huang-Ping Yu ◽

Ya-Ching Hsieh ◽

Mashkoor A. Choudhry ◽

Takao Suzuki ◽

...

Keyword(s):

Estrogen Receptor ◽

Inflammatory Cytokine ◽

Hepatic Injury ◽

Cytokine Production ◽

Inflammatory Cytokine Production ◽

Related Pathway

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