Squalene Stimulates a Key Innate Immune Cell to Foster Wound Healing and Tissue Repair

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2018 Oct 27

PMID 30363968

Citations 18

Authors

Cristina Sanchez-Quesada

Alicia Lopez-Biedma

Estefania Toledo

Jose J Gaforio

Affiliations

Soon will be listed here.

Abstract

Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro- and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF- and NF-B in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing.

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References

Cho S, Choi C, Lee D, Won C, Kim S, Lee S . High-dose squalene ingestion increases type I procollagen and decreases ultraviolet-induced DNA damage in human skin in vivo but is associated with transient adverse effects. Clin Exp Dermatol. 2009; 34(4):500-8. DOI: 10.1111/j.1365-2230.2008.03133.x. View

Estruch R, Ros E, Salas-Salvado J, Covas M, Corella D, Aros F . Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013; 368(14):1279-90. DOI: 10.1056/NEJMoa1200303. View

Xiao L, Aoshima H, Saitoh Y, Miwa N . The effect of squalane-dissolved fullerene-C60 on adipogenesis-accompanied oxidative stress and macrophage activation in a preadipocyte-monocyte co-culture system. Biomaterials. 2010; 31(23):5976-85. DOI: 10.1016/j.biomaterials.2010.04.032. View

Patel V, Kreider B, Li Y, Li H, Leung K, Salcedo T . Molecular and functional characterization of two novel human C-C chemokines as inhibitors of two distinct classes of myeloid progenitors. J Exp Med. 1997; 185(7):1163-72. PMC: 2196270. DOI: 10.1084/jem.185.7.1163. View

Sanchez-Quesada C, Lopez-Biedma A, Gaforio J . Maslinic Acid enhances signals for the recruitment of macrophages and their differentiation to m1 state. Evid Based Complement Alternat Med. 2015; 2015:654721. PMC: 4364129. DOI: 10.1155/2015/654721. View

Guillen N, Acin S, Navarro M, Perona J, Arbones-Mainar J, Arnal C . Squalene in a sex-dependent manner modulates atherosclerotic lesion which correlates with hepatic fat content in apoE-knockout male mice. Atherosclerosis. 2007; 197(1):72-83. DOI: 10.1016/j.atherosclerosis.2007.08.008. View

Coussens L, Werb Z . Inflammation and cancer. Nature. 2002; 420(6917):860-7. PMC: 2803035. DOI: 10.1038/nature01322. View

Aggarwal B, Shishodia S, Sandur S, Pandey M, Sethi G . Inflammation and cancer: how hot is the link?. Biochem Pharmacol. 2006; 72(11):1605-21. DOI: 10.1016/j.bcp.2006.06.029. View

Stetler-Stevenson W . The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2. Cancer Metastasis Rev. 2007; 27(1):57-66. PMC: 2254553. DOI: 10.1007/s10555-007-9105-8. View

10.

Lampinen M, Carlson M, Hakansson L, Venge P . Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy. 2004; 59(8):793-805. DOI: 10.1111/j.1398-9995.2004.00469.x. View

11.

Owen R, Giacosa A, Hull W, Haubner R, Wurtele G, Spiegelhalder B . Olive-oil consumption and health: the possible role of antioxidants. Lancet Oncol. 2002; 1:107-12. DOI: 10.1016/s1470-2045(00)00015-2. View

12.

Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K . IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer. 2015; 112(9):1501-9. PMC: 4453666. DOI: 10.1038/bjc.2015.101. View

13.

Shivappa N, Hebert J, Askari F, Kardoust Parizi M, Rashidkhani B . Increased Inflammatory Potential of Diet is Associated with Increased Risk of Prostate Cancer in Iranian Men. Int J Vitam Nutr Res. 2017; 86(3-4):161-168. DOI: 10.1024/0300-9831/a000395. View

14.

Ito M, Iizuka H, Masuno T, Yasunami R, Ogura T, Yamamura Y . Killing of tumor cells in vitro by macrophages from mice given injections of squalene-treated cell wall skeleton of Nocardia rubra. Cancer Res. 1981; 41(7):2925-30. View

15.

Juhas U, Ryba-Stanislawowska M, Szargiej P, Mysliwska J . Different pathways of macrophage activation and polarization. Postepy Hig Med Dosw (Online). 2015; 69:496-502. DOI: 10.5604/17322693.1150133. View

16.

Kalogeropoulos N, Tsimidou M . Antioxidants in Greek Virgin Olive Oils. Antioxidants (Basel). 2016; 3(2):387-413. PMC: 4665486. DOI: 10.3390/antiox3020387. View

17.

Buckland G, Travier N, Cottet V, Gonzalez C, Lujan-Barroso L, Agudo A . Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer. 2012; 132(12):2918-27. DOI: 10.1002/ijc.27958. View

18.

Covas M . Olive oil and the cardiovascular system. Pharmacol Res. 2007; 55(3):175-86. DOI: 10.1016/j.phrs.2007.01.010. View

19.

Jackson L, Evers B . Chronic inflammation and pathogenesis of GI and pancreatic cancers. Cancer Treat Res. 2006; 130:39-65. DOI: 10.1007/0-387-26283-0_2. View

20.

Heusinkveld M, van der Burg S . Identification and manipulation of tumor associated macrophages in human cancers. J Transl Med. 2011; 9:216. PMC: 3286485. DOI: 10.1186/1479-5876-9-216. View