Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Angiopoietin-like protein 2 may mediate the inflammation in murine mastitis through the activation of interleukin-6 and tumour necrosis factor-α

  • 245 Accesses

  • 3 Citations


Mastitis is the inflammation of the mammary gland. Recent research has shown that Angiopoietin-like protein 2 (ANGPTL2) is a key inflammatory mediator. In the present study, we tested whether there is a correlation between increased ANGPTL2 expression and inflammation in response to Staphylococcus aureus in murine mastitis and the mechanisms involved. Thirty mice were divided into two groups: blank control group, challenged group. The entire infused mammary glands were removed to observe the changes of histopathology, myeloperoxidase (MPO) activity, production of tumour necrosis factor-α (TNF-α) and interleukin (IL)-6, and genes expression of ANGPTL2, TNF-α and IL-6. In challenged group, the structure of mammary glands was damaged and the large areas of cell fragments were observed. The MPO activity, IL-6 and TNF-α concentrations, ANGPTL2, IL-6, and TNF-α mRNA levels were significantly elevated in challenged group compared with blank control group. The present findings indicate ANGPTL2 may mediate the inflammation in murine mastitis through the activation of IL-6 and TNF-α.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. Al-Mousawi AM, Kulp GA, Branski LK, Kraft R, Mecott GA, Williams FN, Herndon DN, Jeschke MG (2010) Impact of anesthesia, analgesia, and euthanasia technique on the inflammatory cytokine profile in a rodent model of severe burn injury. Shock 34(3):261–268

  2. Aoi J, Endo M, Kadomatsu T, Miyata K, Nakano M, Horiguchi H, Ogata A, Odagiri H, Yano M, Araki K, Jinnin M, Ito T, Hirakawa S, Ihn H, Oike Y (2011) Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and metastasis. Cancer Res 71(24):7502–7512. doi:10.1158/0008-5472

  3. Aoi J, Endo M, Kadomatsu T, Miyata K, Ogata A, Horiguchi H, Odagiri H, Masuda T, Fukushima S, Jinnin M, Hirakawa S, Sawa T, Akaike T, Ihn H, Oike Y (2014) Angiopoietin-like protein 2 accelerates carcinogenesis by activating chronic inflammation and oxidative stress. Mol Cancer Res 2:239–249. doi:10.1158/1541-7786

  4. Elazar S, Gonen E, Livneh-Kol A, Rosenshine I, Shpigel NY (2010) Neutrophil recruitment in endotoxin-induced murine mastitis is strictly dependent on mammary alveolar macrophages. Vet Res 41(1):10. doi:10.1051/vetres/2009058

  5. Farhat N, Thorin-Trescases N, Mamarbachi M, Villeneuve L, Yu C, Martel C, Duquette N, Gayda M, Nigam A, Juneau M, Allen BG, Thorin E (2013) Angiopoietin-like 2 promotes atherogenesis in mice. J Am Heart Assoc 3:e000201. doi:10.1161/JAHA.113.000201

  6. Kadomatsu T, Uragami S, Akashi M, Tsuchiya Y, Nakajima H, Nakashima Y, Endo M, Miyata K, Terada K, Todo T, Node K, Oike Y (2013) A molecular clock regulates angiopoietin-like protein 2 expression. PLoS ONE 8(2):e57921. doi:10.1371/journal.pone.0057921

  7. Kanda A, Noda K, Oike Y, Ishida S (2012) Angiopoietin-like protein 2 mediates endotoxin-induced acute inflammation in the eye. Lab Investig 11:1553–1563. doi:10.1038/labinvest

  8. Kushibiki S (2011) Tumor necrosis factor-α-induced inflammatory responses in cattle. Anim Sci J 4:504–511. doi:10.1111/j.1740-0929.2011.00931.x

  9. Li M, Liu X, Robinson G, Bar-Peled U, Wagner KU, Young WS, Hennighausen L, Furth PA (1997) Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc Natl Acad Sci USA 94(7):3425–3430

  10. Li D, Fu Y, Zhang W, Su G, Liu B, Guo M, Li F, Liang D, Liu Z, Zhang X, Cao Y, Zhang N, Yang Z (2013) Salidroside attenuates inflammatory responses by suppressing nuclear factor-κB and mitogen activated protein kinases activation in lipopolysaccharide-induced mastitis in mice. Inflamm Res 1:9–15. doi:10.1007/s00011-012-0545-4

  11. Ogata A, Endo M, Aoi J, Takahashi O, Kadomatsu T, Miyata K, Tian Z, Jinnin M, Fukushima S, Ihn H, Oike Y (2012) The role of angiopoietin-like protein 2 in pathogenesis of dermatomyositis. Biochem Biophys Res Commun 418(3):494–499. doi:10.1016/j.bbrc.2012.01.052

  12. Okada T, Tsukano H, Endo M, Tabata M, Miyata K, Kadomatsu T, Miyashita K, Semba K, Nakamura E, Tsukano M, Mizuta H, Oike Y (2010) Synoviocyte-derived angiopoietin-like protein 2 contributes to synovial chronic inflammation in rheumatoid arthritis. Am J Pathol 176(5):2309–2319. doi:10.2353/ajpath.2010.090865

  13. Rainard P, Cunha P, Bougarn S, Fromageau A, Rossignol C, Gilbert FB, Berthon P (2013) T helper 17-associated cytokines are produced during antigen-specific inflammation in themammary gland. PLoS ONE 8(5):e63471. doi:10.1371/journal.pone.0063471

  14. Sasaki H, Suzuki A, Shitara M, Hikosaka Y, Okuda K, Moriyama S, Yano M, Fujii Y (2012) Angiopoietin-like protein ANGPTL2 gene expression is correlated with lymph node metastasis in lung cancer. Oncol Lett 4(6):1325–1328

  15. Shang H, Wei H, Yue B, Xu P, Huang H (2009) Microsatellite analysis in two populations of Kunming mice. Lab Anim 43(1):34–40. doi:10.1258/la.2008.008098

  16. Song X, Wang T, Zhang Z, Jiang H, Wang W, Cao Y, Zhang N (2015) Anti-inflammatory effect by regulating inflammatory signaling pathways and cytokines in LPS-induced mouse mastitis. Inflammation 38(1):79–88. doi:10.1007/s10753-014-0009-9

  17. Trigo G, Dinis M, França A, Bonifácio Andrade E, Gil da Costa RM, Ferreira P, Tavares D (2009) Leukocyte populations and cytokine expression in the mammary gland in a mouse model of Streptococcus agalactiae mastitis. J Med Microbiol 58(Pt 7):951–958. doi:10.1099/jmm.0.007385-0

  18. Tuchscherr LP, Buzzola FR, Alvarez LP, Caccuri RL, Lee JC, Sordelli DO (2005) Capsule-negative Staphylococcus aureus induces chronic experimental mastitis in mice. Infect Immun 73(12):7932–7937

  19. Zheng J, Watson AD, Kerr DE (2006) Genome-wide expression analysis of lipopolysaccharide-induced mastitis in a mouse model. Infect Immun 74(3):1907–1915

Download references


Project supported by Hunan Provincial Natural Science Foundation of China (14JJ2079).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Correspondence to Hong-Bo Xiao.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Xiao, H., Sun, Z. et al. Angiopoietin-like protein 2 may mediate the inflammation in murine mastitis through the activation of interleukin-6 and tumour necrosis factor-α. World J Microbiol Biotechnol 31, 1235–1240 (2015).

Download citation


  • Angiopoietin-like protein 2
  • Murine mastitis
  • Staphylococcus aureus