Mechanical loading activates the YAP/TAZ pathway and chemokine expression in the MLO-Y4 osteocyte-like cell line

Break-through bleeding is a problem common to many women using long-acting progestin-only contraceptives such as Implanon, and is the main reason many women discontinue using them. Our previous studies (1) identified a number of chemokines (chemoattractive cytokines) that are highly expressed during the menstrual cycle with the capacity to selectively attract the leukocyte subsets present in each phase. Leukocytes produce factors thought to be critical for endometrial breakdown and remodelling, including matrix metalloproteinases (MMPs). We hypothesised that progestins act on endometrial epithelial cells to activate chemokine expression. The chemokines attract leukocytes into the tissue and stimulate their production of MMPs, contributing to tissue breakdown and break-through bleeding. The present study investigated the role of appropriately selected chemokines on leukocyte MMP production. The eosinophilic cell line EOL-1 and the mast cell line HMC1 were treated with four chemokines (fractalkine, HCC-1, MCP-3 and IL-8) at a range of concentrations. MMP production and activation were analysed by gelatin and casein zymography of culture medium. No response was observed from the mast cells under any of the treatments. However, there was a significant increase in latent MMP-9 production by eosinophils in response to increasing concentrations of IL-8 and MCP-3. Results show a greater than 2-fold increase in the amount of latent MMP-9 in response to IL-8 or MCP-3 (300�ng/mL and 80�ng/mL respectively) compared to non-treated controls. These chemokines had no significant effect on levels of active MMP-9 or latent and active forms of MMP-2. HCC-1 and fractalkine had little effect on either MMP-9 or MMP-2 production by these cells. These data support the hypothesis that MMP production by leukocytes is regulated, at least in part, by selective chemokines expressed during menstruation. Future studies will expand the leukocyte subtypes tested and investigate the role of synthetic progestins in chemokine expression from endometrial epithelial cells. (1) Jones R. L. et al. (2003) Proceedings 34th Annual Conference of Society for Reproductive Biology. Reprod. Fertil. Dev. 15 (suppl.), A85.

Download Full-text

Mechanical loading activates YAP/TAZ pathway and chemokines in osteocyte-like cell line MLO-Y4

Bone Reports ◽

10.1016/j.bonr.2021.100914 ◽

2021 ◽

Vol 14 ◽

pp. 100914

Author(s):

Martine Cohen-Solal

Keyword(s):

Cell Line ◽

Mechanical Loading

Download Full-text

Interleukin-1β Regulates CXCL8 Release and Influences Disease Outcome in Response to Streptococcus pneumoniae, Defining Intercellular Cooperation between Pulmonary Epithelial Cells and Macrophages

Infection and Immunity ◽

10.1128/iai.05697-11 ◽

2011 ◽

Vol 80 (3) ◽

pp. 1140-1149 ◽

Cited By ~ 52

Author(s):

Helen M. Marriott ◽

Kate A. Gascoyne ◽

Ravi Gowda ◽

Ian Geary ◽

Martin J. H. Nicklin ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Epithelial Cells ◽

Cell Line ◽

A549 Cells ◽

Neutrophil Recruitment ◽

Molecular Networks ◽

Cellular Interactions ◽

Chemokine Expression ◽

Tnf Α ◽

Cxc Chemokine

The success ofStreptococcus pneumoniae(the pneumococcus) as a pulmonary pathogen is related to its restriction of innate immune responses by respiratory epithelial cells. The mechanisms used to overcome this restriction are incompletely elucidated. Pulmonary chemokine expression involves complex cellular and molecular networks, involving the pulmonary epithelium, but the specific cellular interactions and the cytokines that control them are incompletely defined. We show that serotype 2 or 4 pneumococci induce only modest levels of CXCL8 expression from epithelial cell lines, even in the absence of a polysaccharide capsule. In contrast, coculture of A549 cells with the macrophage-like THP-1 cell line, differentiated with vitamin D, or monocyte-derived macrophages enhanced CXCL8 release. Supernatants from the THP-1 cell line prime A549 cells to release CXCL8 at levels similar to cocultures. Interleukin-1Ra (IL-1Ra) inhibits CXCL8 release from cocultures and reduces the activity of macrophage-conditioned media, but inhibition of tumor necrosis factor alpha (TNF-α) had only a minimal effect on CXCL8 release. Release of IL-1β but not TNF-α was upregulated in cocultures. IL-1 type 1 receptor knockout C57BL/6 and BALB/c mice confirmed the importance of IL-1 signaling in CXC chemokine expression and neutrophil recruitmentin vivo. In fulminant disease, increased IL-1 signaling resulted in increased neutrophils in the airway and more invasive disease. These results demonstrate that IL-1 is an important component of the cellular network involving macrophages and epithelial cells, which facilitates CXC chemokine expression and aids neutrophil recruitment during pneumococcal pneumonia. They also highlight a potential clinical role for anti-IL-1 treatment to limit excessive neutrophilic inflammation in the lung.

Download Full-text