Abstract
Keratocan and lumican are small, leucine-rich repeat KSPGs in the extracellular matrix (ECM) of the mammalian cornea, whose primary role is to maintain corneal transparency. In the current study, we examined the role of these proteoglycans in the breakdown of the chemokine gradient and resolution of corneal inflammation. LPS was injected into the corneal stroma of C57BL/6 mice, and corneal extracts were examined by immunoblot analysis. We found reduced expression of the 52-kD keratocan protein after 6 h and conversely, increased expression of 34/37 kD immunoreactive products. Further, appearance of the 34/37-kD proteins was dependent on neutrophil infiltration to the cornea, as the appearance of these products was coincident with neutrophil infiltration, and the 34/37-kD products were not detected in explanted corneas or in CXCR2 -/- corneas with deficient neutrophil recruitment. Furthermore, the 34/37-kD products and CXCL1/KC were detected in the anterior chamber, into which the corneal stroma drains; and CXCL1/KC was elevated significantly in keratocan-/- and lumican-/- mice. Together, these findings indicate that the inflammatory response in the cornea is regulated by proteoglycan/CXCL1 complexes, and their diffusion into the anterior chamber is consistent with release of a chemokine gradient and resolution of inflammation.
| Original language | English |
|---|---|
| Pages (from-to) | 517-522 |
| Number of pages | 6 |
| Journal | Journal of Leukocyte Biology |
| Volume | 88 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2010 |
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Keywords
- Extracellular matrix
- Keratitis
- Matrix metalloproteinase
ASJC Scopus subject areas
- Cell Biology
- Immunology
Cite this
Regulation of corneal inflammation by neutrophil-dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient. / Carlson, Eric C.; Sun, Yan; Auletta, Jeffery; Kao, Winston W Y; Liu, Chia Yang; Perez Quinones, Victor L; Pearlman, Eric.
In: Journal of Leukocyte Biology, Vol. 88, No. 3, 01.09.2010, p. 517-522.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of corneal inflammation by neutrophil-dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient
AU - Carlson, Eric C.
AU - Sun, Yan
AU - Auletta, Jeffery
AU - Kao, Winston W Y
AU - Liu, Chia Yang
AU - Perez Quinones, Victor L
AU - Pearlman, Eric
PY - 2010/9/1
Y1 - 2010/9/1
N2 - Keratocan and lumican are small, leucine-rich repeat KSPGs in the extracellular matrix (ECM) of the mammalian cornea, whose primary role is to maintain corneal transparency. In the current study, we examined the role of these proteoglycans in the breakdown of the chemokine gradient and resolution of corneal inflammation. LPS was injected into the corneal stroma of C57BL/6 mice, and corneal extracts were examined by immunoblot analysis. We found reduced expression of the 52-kD keratocan protein after 6 h and conversely, increased expression of 34/37 kD immunoreactive products. Further, appearance of the 34/37-kD proteins was dependent on neutrophil infiltration to the cornea, as the appearance of these products was coincident with neutrophil infiltration, and the 34/37-kD products were not detected in explanted corneas or in CXCR2 -/- corneas with deficient neutrophil recruitment. Furthermore, the 34/37-kD products and CXCL1/KC were detected in the anterior chamber, into which the corneal stroma drains; and CXCL1/KC was elevated significantly in keratocan-/- and lumican-/- mice. Together, these findings indicate that the inflammatory response in the cornea is regulated by proteoglycan/CXCL1 complexes, and their diffusion into the anterior chamber is consistent with release of a chemokine gradient and resolution of inflammation.
AB - Keratocan and lumican are small, leucine-rich repeat KSPGs in the extracellular matrix (ECM) of the mammalian cornea, whose primary role is to maintain corneal transparency. In the current study, we examined the role of these proteoglycans in the breakdown of the chemokine gradient and resolution of corneal inflammation. LPS was injected into the corneal stroma of C57BL/6 mice, and corneal extracts were examined by immunoblot analysis. We found reduced expression of the 52-kD keratocan protein after 6 h and conversely, increased expression of 34/37 kD immunoreactive products. Further, appearance of the 34/37-kD proteins was dependent on neutrophil infiltration to the cornea, as the appearance of these products was coincident with neutrophil infiltration, and the 34/37-kD products were not detected in explanted corneas or in CXCR2 -/- corneas with deficient neutrophil recruitment. Furthermore, the 34/37-kD products and CXCL1/KC were detected in the anterior chamber, into which the corneal stroma drains; and CXCL1/KC was elevated significantly in keratocan-/- and lumican-/- mice. Together, these findings indicate that the inflammatory response in the cornea is regulated by proteoglycan/CXCL1 complexes, and their diffusion into the anterior chamber is consistent with release of a chemokine gradient and resolution of inflammation.
KW - Extracellular matrix
KW - Keratitis
KW - Matrix metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=77957111508&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957111508&partnerID=8YFLogxK
U2 - 10.1189/jlb.0310134
DO - 10.1189/jlb.0310134
M3 - Article
C2 - 20495072
AN - SCOPUS:77957111508
VL - 88
SP - 517
EP - 522
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 3
ER -