PMID- 32323751
OWN - NLM
STAT- MEDLINE
DCOM- 20210120
LR  - 20211204
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 45
IP  - 6
DP  - 2020 Jun
TI  - Sulforaphane reduces intracellular survival of Staphylococcus aureus in 
      macrophages through inhibition of JNK and p38 MAPK‑induced inflammation.
PG  - 1927-1941
LID - 10.3892/ijmm.2020.4563 [doi]
AB  - Macrophages are active contributors to the innate immune defense system. As 
      macrophage activation is clearly affected by the surrounding microenvironment, 
      the present study investigated the effect of sulforaphane (SFN) on the 
      bactericidal activity of macrophages and the underlying molecular mechanisms 
      involved in this process. Human THP‑1‑derived macrophages, primary human 
      peripheral blood mononuclear cell‑derived macrophages, and primary mouse bone 
      marrow derived‑macrophages (BMDMs) pretreated with SFN or DMSO were utilized in a 
      model of Staphylococcus aureus infection. The results suggested that SFN 
      pretreatment of macrophages effectively repressed the intracellular survival of 
      S. aureus through modulation of p38/JNK signaling and decreased S. aureus‑induced 
      caspases‑3/7‑dependent cell apoptosis, potentially through downregulation of 
      microRNA (miR)‑142‑5p and miR‑146a‑5p. As SFN is a well‑known activator of 
      nuclear factor erythroid 2‑related factor 2 (Nrf2), Nrf2‑/‑ BMDMs were used to 
      demonstrate that the SFN‑mediated inhibitory effect was independent of Nrf2. 
      Nevertheless, an increase in intracellular bacterial survival in Nrf2‑deficient 
      macrophages was observed. In addition, SFN pretreatment suppressed 
      S. aureus‑induced transcriptional expression of genes coding for the 
      proinflammatory cytokines interleukin (IL)‑1beta, IL‑6, and tumor necrosis 
      factor‑alpha (TNF‑alpha), as well as for the M1 markers C‑C motif chemokine receptor 7, 
      IL‑23 and inducible nitric oxide synthase (iNOS). Western blot analysis indicated 
      that S. aureus challenge activated p38 mitogen‑activated protein kinase (MAPK) 
      (p38) and c‑Jun N‑terminal kinase (JNK) MAPK signaling pathways, while SFN 
      pretreatment prevented p38 and JNK phosphorylation. Pretreatment with 2 specific 
      inhibitors of p38 and JNK, SB203580 and SP600125, respectively, resulted in a 
      decrease in S. aureus‑induced proinflammatory gene expression levels compared 
      with those observed in the SFN‑pretreated macrophages. Furthermore, THP‑1‑derived 
      macrophages pretreated with SB203580 or SP600125 prior to bacterial infection 
      exhibited a significant inhibition in intracellular S. aureus survival. In 
      conclusion, we hypothesize that concomitant targeting of the p38/JNK‑inflammatory 
      response and the S. aureus‑induced apoptosis with SFN may be a promising 
      therapeutic approach in S. aureus infection.
FAU - Deramaudt, Therese B
AU  - Deramaudt TB
AD  - Department of Neuromuscular Handicap: Biotherapies and Therapeutic Innovations, 
      National Institute of Health and Medical Research, University of 
      Versailles‑Saint‑Quentin‑en‑Yvelines, 78180 Montigny‑le‑Bretonneux, France.
FAU - Ali, Malika
AU  - Ali M
AD  - Department of Neuromuscular Handicap: Biotherapies and Therapeutic Innovations, 
      National Institute of Health and Medical Research, University of 
      Versailles‑Saint‑Quentin‑en‑Yvelines, 78180 Montigny‑le‑Bretonneux, France.
FAU - Vinit, Stephane
AU  - Vinit S
AD  - Department of Neuromuscular Handicap: Biotherapies and Therapeutic Innovations, 
      National Institute of Health and Medical Research, University of 
      Versailles‑Saint‑Quentin‑en‑Yvelines, 78180 Montigny‑le‑Bretonneux, France.
FAU - Bonay, Marcel
AU  - Bonay M
AD  - Department of Neuromuscular Handicap: Biotherapies and Therapeutic Innovations, 
      National Institute of Health and Medical Research, University of 
      Versailles‑Saint‑Quentin‑en‑Yvelines, 78180 Montigny‑le‑Bretonneux, France.
LA  - eng
PT  - Journal Article
DEP - 20200401
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Isothiocyanates)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sulfoxides)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - GA49J4310U (sulforaphane)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Inflammation/*drug therapy/genetics/metabolism
MH  - Isothiocyanates/*pharmacology
MH  - MAP Kinase Kinase 4/*antagonists & inhibitors/metabolism
MH  - MAP Kinase Signaling System/*drug effects
MH  - Macrophages/drug effects/*microbiology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Staphylococcal Infections/drug therapy/metabolism
MH  - Staphylococcus aureus/*drug effects
MH  - Sulfoxides
MH  - THP-1 Cells
PMC - PMC7169961
EDAT- 2020/04/24 06:00
MHDA- 2021/01/21 06:00
PMCR- 2020/04/01
CRDT- 2020/04/24 06:00
PHST- 2019/09/20 00:00 [received]
PHST- 2020/02/11 00:00 [accepted]
PHST- 2020/04/24 06:00 [pubmed]
PHST- 2021/01/21 06:00 [medline]
PHST- 2020/04/24 06:00 [entrez]
PHST- 2020/04/01 00:00 [pmc-release]
AID - ijmm-45-06-1927 [pii]
AID - 10.3892/ijmm.2020.4563 [doi]
PST - ppublish
SO  - Int J Mol Med. 2020 Jun;45(6):1927-1941. doi: 10.3892/ijmm.2020.4563. Epub 2020 
      Apr 1.