CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor
Wei-Yu Lee1, Chun-Jen Wang, Ting-Yu Lin
1Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
Abstract:
Chemokines play pivotal roles in the recruitment of various immune cells to diverse tissues in both physiological and pathological conditions. CXCL17 is an orphan chemokine preliminarily found to be involved in tumor angiogenesis. However, its protein nature, as well as its endogenous bioactivity, has not been well clarified. Using real-time PCR, immunohistochemical staining, and Western blotting, we found that CXCL17 is highly expressed in both a constitutive and inducible manner in the rat gastric mucosa, where it undergoes endoproteolysis during protein maturation. The mature CXCL17 exhibited strong chemoattractant abilities targeting monocytes and macrophages, potentially through ERK1/2 and p38 but not JNK signaling. CXCL17 also induced the production of proangiogenic factors such as vascular endothelial growth factor A from treated monocytes. Furthermore, in contrast to other CXC chemokines that accelerate inflammatory responses, CXCL17 showed novel anti-inflammatory effects on LPS-activated macrophages. Therefore, our data suggest that CXCL17 in the gastric lamina propria may play an important role in tissue repair and anti-inflammation, both of which help to maintain the integrity of the gastric mucosa.
Insights
CXCL17, a novel chemokine, attracts monocytes and macrophages to the gastric mucosa, promoting tissue repair and anti-inflammation. This finding reveals its potential role in maintaining gastric integrity.
Area of Science:
- Immunology
- Molecular Biology
- Gastroenterology
Background:
- Chemokines are crucial for immune cell trafficking in physiological and pathological states.
- CXCL17, an orphan chemokine, has preliminary links to tumor angiogenesis, but its function is unclear.
- Understanding CXCL17's endogenous role is vital for comprehending immune responses in tissues.
Purpose of the Study:
- To elucidate the protein nature and endogenous bioactivity of CXCL17 in the gastric mucosa.
- To investigate CXCL17's chemoattractant properties and signaling pathways.
- To explore CXCL17's effects on immune cell function and inflammatory responses.
Main Methods:
- Real-time PCR and Western blotting were used to assess CXCL17 expression.
- Immunohistochemical staining identified CXCL17 localization in rat gastric mucosa.
- Monocyte/macrophage assays examined chemoattraction, signaling pathways (ERK1/2, p38, JNK), and cytokine production.
Main Results:
- CXCL17 is constitutively and inducibly expressed in rat gastric mucosa, undergoing endoproteolysis.
- Mature CXCL17 chemoattracts monocytes and macrophages via ERK1/2 and p38 signaling.
- CXCL17 induces proangiogenic factors and exhibits anti-inflammatory effects on activated macrophages.
Conclusions:
- CXCL17 plays a significant role in immune cell recruitment within the gastric lamina propria.
- CXCL17 possesses chemoattractant, proangiogenic, and anti-inflammatory functions.
- CXCL17 contributes to tissue repair and anti-inflammation, supporting gastric mucosal integrity.
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