2. Academic Validation
  3. Tricarbonyldichlororuthenium(II) dimer, the lipid-soluble carbon monoxide-releasing molecule, attenuates Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages

Tricarbonyldichlororuthenium(II) dimer, the lipid-soluble carbon monoxide-releasing molecule, attenuates Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages

  • Int Immunopharmacol. 2021 Jan:90:107190. doi: 10.1016/j.intimp.2020.107190.
Eun-Young Choi 1,  Bo Ram Keum 1,  So-Hui Choe 1,  Jin-Yi Hyeon 1,  In Soon Choi 1,  Sung-Jo Kim 2
Affiliations

Affiliations

  • 1 Department of Biological Science, College of Medical and Life Sciences, Silla University, 140 Baegyang-daero, 700beon-gil, Sasang-gu, Busan 617-736, Republic of Korea.
  • 2 Department of Periodontology, School of Dentistry, Pusan National University, 49 Busandaehak-ro, Mulgeum-eup, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea; Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Gyeongsangnam-do, Republic of Korea; Dental and Life Science Institute, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea. Electronic address: sungjokim@pusan.ac.kr.
PMID: 33223468 DOI: 10.1016/j.intimp.2020.107190
Abstract

Carbon monoxide (CO) is increasingly being appreciated as an important mediator that has pleiotropic biological properties and appears to have a possible therapeutic application for a variety of disorders. Nevertheless, whether this gaseous molecule may be utilized as a therapeutic intervention for periodontal disease is unclear. Here, we examined the potential beneficial effect of CO-releasing molecule-2 (CORM-2), a tricarbonyldichlororuthenium(II) dimer, against the elaboration of proinflammatory mediators by murine macrophages challenged with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogenic bacterium implicated in inflammatory periodontal disease. We found that NO and IL-1β production, iNOS protein expression and mRNA expressions of iNOS and IL-1β were significantly down-regulated when LPS-challenged RAW264.7 cells were exposed to CORM-2. In addition, HO-1 expression was upregulated by CORM-2 in cells activated with P. intermedia LPS, and the inhibitory influence of CORM-2 upon NO production was attenuated by tin protoporphyrin IX, an inhibitor of HO activity. PPAR-γ did not function in the attenuation of NO and IL-1β by CORM-2. JNK and p38 phosphorylation caused by LPS was not altered by CORM-2. CORM-2 reduced NF-κB reporter activity and IκB-α degradation elicited by P. intermedia LPS. Additionally, CORM-2 inhibited LPS-induced phosphorylation of STAT1/3. In conclusion, CORM-2 suppresses NO and IL-1β production caused by P. intermedia LPS. CORM-2 exerts its effect by a mechanism involving anti-inflammatory HO-1 induction and attenuation of NF-κB and STAT1/3 activation, independently of PPAR-γ as well as JNK and p38. CORM-2 may hold promise as host response modulation agent for periodontal disease, though further research is indicated to verify the therapeutic effect.

Keywords

Interleukin-1β; Lipopolysaccharide; Nitric oxide; Periodontal disease; Prevotella intermedia; Tricarbonyldichlororuthenium(II) dimer.

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