PMID- 38287119
OWN - NLM
STAT- MEDLINE
DCOM- 20240131
LR  - 20240206
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Jan 29
TI  - The clarithromycin-binding proteins NIPSNAP1 and 2 regulate cytokine production 
      through mitochondrial quality control.
PG  - 2354
LID - 10.1038/s41598-024-52582-7 [doi]
LID - 2354
AB  - The mechanism underlying the anti-inflammatory effect of macrolide antibiotics, 
      such as clarithromycin (CAM), remains to be clarified. The CAM-binding proteins 
      4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 
      25 (SNAP25)-like protein homolog (NIPSNAP) 1 and 2 are involved in the immune 
      response and mitochondrial homeostasis. However, the axis between 
      CAM-NIPSNAP-mitochondria and Toll-like receptor (TLR) and their molecular 
      mechanisms remain unknown. In this study, we sought to elucidate the relationship 
      between mitochondrial homeostasis mediated by NIPSNAP1 and 2 and the 
      immunomodulatory effect of CAM. NIPSNAP1 or 2 knockdown (KD) by RNA interference 
      impaired TLR4-mediated interleukin-8 (IL-8) production. Similar impairment was 
      observed upon treatment with mitochondrial function inhibitors. However, IL-8 
      secretion was not impaired in NIPSNAP1 and 2 individual knockout (KO) and double 
      KO (DKO) cells. Moreover, the oxygen consumption rate (OCR) in mitochondria 
      measured using a flex analyzer was significantly reduced in NIPSNAP1 or 2 KD 
      cells, but not in DKO cells. CAM also dose-dependently reduced the OCR. These 
      results indicate that CAM suppresses the IL-8 production via the mitochondrial 
      quality control regulated by temporary functional inhibition of NIPSNAP1 and 2. 
      Our findings provide new insight into the mechanisms underlying cytokine 
      production, including the TLR-mitochondria axis, and the immunomodulatory effects 
      of macrolides.
CI  - (c) 2024. The Author(s).
FAU - Yamamoto, Soh
AU  - Yamamoto S
AD  - Department of Microbiology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Ogasawara, Noriko
AU  - Ogasawara N
AD  - Department of Microbiology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan. ogasawara.n@sapmed.ac.jp.
AD  - Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University 
      School of Medicine, Sapporo, Japan. ogasawara.n@sapmed.ac.jp.
FAU - Mitsuhashi, Yukari
AU  - Mitsuhashi Y
AD  - Department of Microbiology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Takano, Kenichi
AU  - Takano K
AD  - Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University 
      School of Medicine, Sapporo, Japan.
FAU - Yokota, Shin-Ichi
AU  - Yokota SI
AD  - Department of Microbiology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
LA  - eng
GR  - 19K07168/Japan Society for the Promotion of Science/
GR  - 18K09381/Japan Society for the Promotion of Science/
GR  - 20H03488/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20240129
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - H1250JIK0A (Clarithromycin)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - *Carrier Proteins/metabolism
MH  - *Membrane Proteins/genetics/metabolism
MH  - Clarithromycin/pharmacology
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Interleukin-8/metabolism
MH  - Toll-Like Receptors/metabolism
MH  - Mitochondria/metabolism
PMC - PMC10824736
COIS- The authors declare no competing interests.
EDAT- 2024/01/30 00:42
MHDA- 2024/01/31 06:43
PMCR- 2024/01/29
CRDT- 2024/01/29 23:31
PHST- 2023/09/26 00:00 [received]
PHST- 2024/01/20 00:00 [accepted]
PHST- 2024/01/31 06:43 [medline]
PHST- 2024/01/30 00:42 [pubmed]
PHST- 2024/01/29 23:31 [entrez]
PHST- 2024/01/29 00:00 [pmc-release]
AID - 10.1038/s41598-024-52582-7 [pii]
AID - 52582 [pii]
AID - 10.1038/s41598-024-52582-7 [doi]
PST - epublish
SO  - Sci Rep. 2024 Jan 29;14(1):2354. doi: 10.1038/s41598-024-52582-7.