C-C motif chemokine ligand 2 induces proliferation and prevents lipopolysaccharide-induced inflammatory responses in bovine mammary epithelial cells

Changwon Yang, Whasun Lim, Hyocheol Bae, Fuller W. Bazer, Gwonhwa Song

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


C-C motif chemokine ligand 2 (CCL2) is a small chemokine which belongs to the CC-type chemokine family, and has chemoattractant activity for recruitment of monocytes to sites of inflammation. Overexpressed CCL2 binding to its receptor C-C chemokine receptor 2 increases the risk of breast cancer in humans, but its effects on proliferation of bovine mammary epithelial cells is not known. Maintaining a high level of proliferative activity in bovine mammary epithelial cells during lactation is important for improving milk yield and can benefit the dairy industry economically. In the present study, we demonstrated that CCL2 induces proliferation of MAC-T cells, a bovine mammary epithelial cell line, and stimulates progression of the cell cycle through stimulation of expression of cyclin D1. Moreover, CCL2 activates phosphoinositide 3-kinase (PI3K)/AKT [AKT, P70-S6 kinase 1 (P70S6K), ribosomal protein S6 (S6)] and mitogen activated protein kinase (MAPK) [extracellular signal-regulated kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and P38] pathways, which are involved in proliferation of MAC-T cells, as evidenced by co-treatment of MAC-T cells with pharmacological inhibitors of cell signaling transcription factors including Wortmannin, U0126, and SP600125. The CCL2 in MAC-T cells attenuates endoplasmic reticulum stress induced by tunicamycin, suggesting that CCL2 regulates intracellular synthesis of proteins and lipids and prevents activation of apoptotic pathways initiated in response to endoplasmic reticulum stress. Furthermore, CCL2 is involved in alleviating lipopolysaccharide (LPS)-induced inflammatory responses in MAC-T cells by reducing LPS-induced expression of IL8, IL6, and nuclear factor kappa B subunit 1 (NFKB1). Collectively, CCL2 is a novel target for improving the quantity and quality of milk from cows through stimulation of proliferation on mammary epithelial cells and attenuation of LPS-induced inflammatory responses.

Original languageEnglish
Pages (from-to)4527-4541
Number of pages15
JournalJournal of Dairy Science
Issue number5
StatePublished - May 2018

Bibliographical note

Funding Information:
This research was supported by a Korea University Grant and we also appreciate School of Life Sciences and Biotechnology for BK21 PLUS, Korea University for supporting the publication fee.

Publisher Copyright:
© 2018 American Dairy Science Association


  • bovine mammary epithelial cells
  • CCL2
  • ER stress
  • inflammation
  • proliferation


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