Differential expression of thymus- and activation-regulated chemokine (CCL17) and macrophage-derived chemokine (CCL22) by human fibroblasts from cornea, skin, and lung.
BACKGROUND
Allergic diseases of the ocular surface, skin, and lung are triggered by T(H)2 cells, which are recruited by thymus- and activation-regulated chemokine (TARC; CCL17) and macrophage-derived chemokine (MDC; CCL22). Resident fibroblasts are thought to contribute to inflammatory cell infiltration through chemokine production.


OBJECTIVE
We sought to provide insight into the clinical differences apparent among these allergic diseases of the eye, skin, and lung, and we compared the abilities of corneal, dermal, and lung fibroblasts to produce TARC and MDC.


METHODS
The amounts of chemokines released into the culture supernatant were determined by means of ELISA, and the intracellular abundance of chemokine mRNAs was quantitated by means of reverse transcription and real-time PCR analysis.


RESULTS
Neither TNF-alpha, IFN-gamma, IL-4, nor IL-13 alone induced the release of TARC from or affected the amount of TARC mRNA in corneal, dermal, or lung fibroblasts. The combination of TNF-alpha with either IL-4 or IL-13, however, markedly increased both TARC release and the abundance of TARC mRNA in corneal and dermal fibroblasts, but not in lung fibroblasts. Neither MDC release nor MDC mRNA was detected in any of the 3 types of fibroblasts stimulated with any of the cytokines examined.


CONCLUSIONS
These results indicate that cytokine regulation of TARC expression differs among fibroblasts derived from the cornea, skin, or lung. Corneal and dermal fibroblasts might thus be important sources of TARC during allergic inflammation.
Fukuda
Ken
K
Department of Ocular Pathophysiology, Yamaguchi University School of Medicine, Ube City, Yamaguchi, Japan.
Fujitsu
Youichiro
Y
Seki
Keisuke
K
Kumagai
Naoki
N
Nishida
Teruo
T
D002478:Cells, Cultured; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism*
C106230:CCL17 protein, human; C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D016207:Cytokines; D004338:Drug Combinations; D012333:RNA, Messenger