PMID- 34445121
OWN - NLM
STAT- MEDLINE
DCOM- 20210916
LR  - 20210916
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 16
DP  - 2021 Aug 5
TI  - Integrin alphav and Vitronectin Prime Macrophage-Related Inflammation and Contribute 
      the Development of Dry Eye Disease.
LID - 10.3390/ijms22168410 [doi]
LID - 8410
AB  - Cell signaling mediated by the alphav integrin plays a pivotal role in macrophage 
      activation in various inflammatory processes, but its involvement in the 
      pathogenesis of dry eye disease (DED) remains unclear. In a murine model of DED, 
      we found increased alphav integrin expression in ocular surface macrophages. The alphav 
      integrins inhibitor c(RGDfK) ameliorated the corneal damage caused by DED, 
      suggesting a pathogenic role for alphav integrin. Because tear hyperosmolarity 
      induces ocular inflammation in DED, a hyperosmolar culture of murine bone 
      marrow-derived macrophages (BMDMs) is used to reproduce inflammation in vitro. 
      However, the expression of proinflammatory cytokine mRNA was minimal, even though 
      alphav integrin was induced. In searching for components that are involved in alphav 
      integrin-mediated inflammation but that are missing from the culture model, we 
      showed that the levels of vitronectin (VTN), a binding ligand of alphav integrins, 
      were increased in the tear fluid and conjunctival stroma of DED animals. The 
      addition of VTN prominently enhanced hyperosmolarity-induced inflammation in 
      BMDMs. Mechanistically, we showed that VTN/alphav integrins mediated NF-kappaB activation 
      to induce inflammatory gene expression in the BMDMs. Our findings indicate that 
      interaction the of VTN with alphav integrins is a crucial step in the inflammatory 
      process in DED and suggests a novel therapeutic target.
FAU - Ho, Tsung-Chuan
AU  - Ho TC
AD  - Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, 
      Taiwan.
FAU - Yeh, Shu-I
AU  - Yeh SI
AD  - Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan.
AD  - Department of Ophthalmology, Mackay Memorial Hospital, Taipei 10449, Taiwan.
FAU - Chen, Show-Li
AU  - Chen SL
AD  - Department and Graduate Institute of Microbiology, College of Medicine, National 
      Taiwan University, Taipei 10617, Taiwan.
FAU - Tsao, Yeou-Ping
AU  - Tsao YP
AD  - Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, 
      Taiwan.
AD  - Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan.
AD  - Department of Ophthalmology, Mackay Memorial Hospital, Taipei 10449, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20210805
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Cytokines)
RN  - 0 (Integrin alphaV)
RN  - 0 (Vitronectin)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Dry Eye Syndromes/*metabolism
MH  - Eye/metabolism
MH  - Female
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Integrin alphaV/*metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Signal Transduction/physiology
MH  - THP-1 Cells
MH  - Tears/metabolism
MH  - Vitronectin/*metabolism
PMC - PMC8395123
OTO - NOTNLM
OT  - c(RGDfK)
OT  - dry eye disease
OT  - inflammation
OT  - macrophage
OT  - vitronectin
OT  - alphav integrin
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/28 06:00
MHDA- 2021/09/18 06:00
PMCR- 2021/08/05
CRDT- 2021/08/27 01:22
PHST- 2021/07/09 00:00 [received]
PHST- 2021/07/31 00:00 [revised]
PHST- 2021/08/03 00:00 [accepted]
PHST- 2021/08/27 01:22 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2021/08/05 00:00 [pmc-release]
AID - ijms22168410 [pii]
AID - ijms-22-08410 [pii]
AID - 10.3390/ijms22168410 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Aug 5;22(16):8410. doi: 10.3390/ijms22168410.