Investigation of Modulatory Effect of Pinolenic Acid (PNA) on Inflammatory Responses in Human THP-1 Macrophage-Like Cell and Mouse Models

Szu Jung Chen, Wen Cheng Huang, Hung Jing Shen, Ruei Yu Chen, Hsiang Chang, Yun Shan Ho, Po Jung Tsai, Lu Te Chuang

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Abstract

Pinolenic acid (PNA) is a rare n-6 polyunsaturated fatty acid (n-6 PUFA) originally identified in pine seeds. Previous studies demonstrated that PNA and its elongation metabolite, Δ7-eicosatrienoic acid (Δ7-ETrA), exerted an anti-inflammatory effect in cultured cells by suppressing prostaglandin E2 (PGE2) production. The objective of this study was to further examine the in vivo anti-inflammatory properties of PNA. Using human THP-1 macrophage, we first confirmed that incorporation of PNA into cellular phospholipids suppressed the production of interleukin-6 (IL-6) (by 46%), tumor necrosis factor-α (TNF-α) (by 18%), and prostaglandin E2 (PGE2) (by 87%), and the expression of type-2 cyclooxygenase (COX-2) (by 27%). Furthermore, we demonstrated that injection of PNA or Δ7-ETrA suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, as measured by ear thickness (by 15%) and biopsy weight (by up to 29%). Both PUFA also lowered proportions of infiltrated leukocytes, neutrophils, and macrophages using flow cytometric analysis. Topical application of PNA or Δ7-ETrA on mouse back skin suppressed TPA-induced pro-inflammatory mediator production, including IL-1β, IL-6, TNF-α, and PGE2, as well as the phosphorylation of p38- and JNK-mitogen-activated protein kinase (MAPK), but not that of ERK-MAPK. That no PNA or Δ7-ETrA was detected in the ear disc after the PUFA injection suggests that their anti-inflammatory effect might not be due to fatty acid incorporation, but to modulation of cell signaling. In conclusion, PNA and Δ7-ETrA exerted the in vivo anti-inflammatory effect by suppressing mouse ear edema and dorsal skin inflammation.

Original languageEnglish
JournalInflammation
DOIs
Publication statusAccepted/In press - 2019 Jan 1
Externally publishedYes

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Keywords

  • inflammation
  • mouse ear edema
  • pinolenic acid (PNA)
  • polyunsaturated fatty acids (PUFA)
  • Δ7-eicosatrienoic acid (Δ7-ETrA)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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