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Peer-reviewedCC BY 4.0Frontiers in Immunology

The p38 MAPK/MSK1/NF-κB axis in chronic prostatitis/chronic pelvic pain syndrome: a testable hypothesis for innate immune inflammatory amplification

  • Yihang Shen1,2
  • Baojun Ju1
  1. 1Department of Andrology, The First Affiliated Hospital of Henan University of Chinese Medicine
  2. 2The First Clinical Medical College, Henan University of Chinese Medicine
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Abstract

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a heterogeneous clinical syndrome that includes NIH category IIIA (inflammatory) and IIIB (noninflammatory) presentations, with pelvic pain, urinary symptoms, sexual dysfunction, and variable immune findings.

Aim: To evaluate whether a p38 MAPK/MSK1/NF-κB network could amplify innate immune signaling in an immune-active subset of CP/CPPS.

Evidence synthesis: Human evidence for coordinated p38, MSK1, and NF-κB activation in CP/CPPS is currently incomplete. p38 MAPK and NF-κB findings from prostatitis models and prostate-cell experiments provide disease-relevant support, whereas most MSK1, chromatin, mitochondrial-DAMP, and long-term inflammatory-memory links are extrapolated from non-prostatic inflammatory systems. MSK1 is activated by both p38 and ERK1/2 and has anti-inflammatory MSK1/2–DUSP1/IL-10 feedback functions; p65 Ser276 is one regulatory checkpoint among several NF-κB controls.

Conclusions: The proposed MSK1-dependent amplification loop is a testable hypothesis rather than a demonstrated CP/CPPS mechanism. Patient-tissue phosphoproteomics, cell-resolved transcriptomics and ATAC-seq, and phenotype-stratified intervention studies are needed before therapeutic claims can be made. No proposed p38, MSK1, Nrf2, NOX, or NLRP3 strategy currently has established clinical efficacy in CP/CPPS.

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Cite

BibTeXRIS
BibTeX
@article{shen2026mapkmsk1nfκb,
  title = {{The p38 MAPK/MSK1/NF-κB axis in chronic prostatitis/chronic pelvic pain syndrome: a testable hypothesis for innate immune inflammatory amplification}},
  author = {Yihang Shen and Baojun Ju},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1955957},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1955957/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The p38 MAPK/MSK1/NF-κB axis in chronic prostatitis/chronic pelvic pain syndrome: a testable hypothesis for innate immune inflammatory amplification
AU  - Yihang Shen
AU  - Baojun Ju
PY  - 2026
DA  - 2026/10/29
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1955957
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1955957/full
AB  - Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a heterogeneous clinical syndrome that includes NIH category IIIA (inflammatory) and IIIB (noninflammatory) presentations, with pelvic pain, urinary symptoms, sexual dysfunction, and variable immune findings.  Aim: To evaluate whether a p38 MAPK/MSK1/NF-κB network could amplify innate immune signaling in an immune-active subset of CP/CPPS.  Evidence synthesis: Human evidence for coordinated p38, MSK1, and NF-κB activation in CP/CPPS is currently incomplete. p38 MAPK and NF-κB findings from prostatitis models and prostate-cell experiments provide disease-relevant support, whereas most MSK1, chromatin, mitochondrial-DAMP, and long-term inflammatory-memory links are extrapolated from non-prostatic inflammatory systems. MSK1 is activated by both p38 and ERK1/2 and has anti-inflammatory MSK1/2–DUSP1/IL-10 feedback functions; p65 Ser276 is one regulatory checkpoint among several NF-κB controls.  Conclusions: The proposed MSK1-dependent amplification loop is a testable hypothesis rather than a demonstrated CP/CPPS mechanism. Patient-tissue phosphoproteomics, cell-resolved transcriptomics and ATAC-seq, and phenotype-stratified intervention studies are needed before therapeutic claims can be made. No proposed p38, MSK1, Nrf2, NOX, or NLRP3 strategy currently has established clinical efficacy in CP/CPPS.
SN  - 1664-3224
ER  -