Investigation of Modulatory Effect of Pinolenic Acid (PNA) on Inflammatory Responses in Human THP-1 Macrophage-Like Cell and Mouse Models
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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.
KEY WORDSpinolenic acid (PNA) Δ7-eicosatrienoic acid (Δ7-ETrA) polyunsaturated fatty acids (PUFA) inflammation mouse ear edema
The authors are grateful to Professor Robert H. Glew, PhD, for editing our manuscript.
This work was supported in part by research grants from the Ministry of Science and Technology, Executive Yuan, Taiwan (MOST 104-2320-B-264-002- and MOST 105-2320-B-264-001) and the Tao Yuan General Hospital, Ministry of Health and Welfare, The Executive Yuan, Taiwan (PTH10408), respectively.
Compliance with Ethical Standards
All procedures were approved by the Institutional Animal Care and Use Committee of Yuanpei University of Medical Technology (IACUC Approval No. LAC10301).
Conflict of Interest
The authors declare that they have no conflict of interest.
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