Herpes Virus Entry Mediator (HVEM) Expression Promotes Inflammation/ Organ Injury in Response to Experimental Indirect-Acute Lung Injury.

Abstract

Therapeutic interventions to treat acute lung injury (ALI) remain largely limited to lung-protective strategies, as a real molecular pathophysiologically driven therapeutic intervention has yet to become available. While we have previously documented the expression of herpes virus entry mediator (HVEM) on leukocytes of septic mice and critically ill patients, its functional role in shock/sepsis-induced ALI has not yet been studied. Inasmuch, a murine model of indirect ALI (iALI) was induced by hemorrhagic shock (HEM) followed by cecal ligation and puncture (CLP), septic challenge and HVEM-siRNA or phosphate buffered saline was administrated by intratracheal instillation 2 h after hemorrhage to determine the role of HVEM in the development of experimental iALI. Indices of lung injury were measured. HVEM expression was significantly elevated in iALI mice. Compared with phosphate buffered saline treated iALI mice, HVEM knock-down by siRNA caused a reduction of cytokine/chemokine levels, myeloperoxidase activity, broncho-alveolar lavage fluid (BALF) cell count and protein concentration. HVEM-siRNA treatment reduced inflammation and attenuated pulmonary architecture destruction as well as provided an early (60 h post HEM-CLP) survival benefit in iALI mice. This ability of anti-HVEM treatment to prevent the development of iALI and provide a transient survival benefit implies that mitigating signaling through HVEM may be a novel target worth further investigation.

• Authors: Tingting Cheng, Jianwen Bai, Chun-Shiang Chung, Yaping Chen, Eleanor A Fallon, Alfred Ayala
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 51 Issue 4 Pg. 487-494 (04 2019) ISSN: 1540-0514 [Electronic] United States
• PMID: 30531604 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• RNA, Small Interfering
• Receptors, Tumor Necrosis Factor, Member 14
• Peroxidase

Topics

• Acute Lung Injury (immunology, metabolism)
• Animals
• Blotting, Western
• Flow Cytometry
• Inflammation (immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Peroxidase (metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Receptors, Tumor Necrosis Factor, Member 14 (genetics, metabolism)
• Sepsis (immunology, metabolism)
• Virus Internalization