Elucidating the role of interleukin 1beta and prostaglandin E2 in upper airway mucosal wound healing.
OBJECTIVE
To determine whether (1) inflammatory mediators IL-1beta (interleukin 1beta) and prostaglandin E2 (PGE2) in mucosal secretions correlate with subglottic mucosal injury; and (2) mucosal fibroblasts contribute to PGE2 production during mucosal healing.


METHODS
The subglottic mucosa in rabbits was wounded by means of varied carbon dioxide laser power and duration. Subglottic fibroblasts were exposed to IL-1beta and assayed for production of PGE2.


METHODS
Thirty-eight New Zealand white rabbits were used. Fibroblasts from normal and pathologic human subglottic tissues were grown in culture.


METHODS
Subglottic injury was established in 29 rabbits, and 9 rabbits were sham-wounded. Subglottic mucosal secretions were collected at baseline and days 1, 3, 7, 14, and 21 postoperatively and assayed for IL-1beta and PGE2 by enzyme-linked immunosorbent assay. Tissue was analyzed using quantitative polymerase chain reaction. Fibroblast cultures were exposed to IL-1beta and analyzed for PGE2 and its synthetic enzymes.


RESULTS
Subglottic injury was associated with increased levels of IL-1beta and PGE2 in secretions. More extensive mucosal injury resulted in higher PGE2 levels at earlier times. Levels of IL-1beta were maximal after lesser damage. Expression of IL-beta and cyclo-oxygenase 2 was elevated after mucosal injury. Fibroblast treatment with IL-1beta resulted in translocation of nuclear factor kappaB, up-regulation of PGE2 synthetic enzymes, and increased production of endogenous PGE2.


CONCLUSIONS
Mucosal injury is associated with up-regulation of inflammatory genes and parallel increases in secretion levels of IL-1beta and PGE2, key mediators of inflammation and healing. Subglottic mucosal fibroblasts are a potential source of inflammatory mediators after injury or other trauma.
Sandulache
Vlad C
VC
Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, PA 15213, USA.
Chafin
J Brett
JB
Li-Korotky
Ha-Sheng
HS
Otteson
Todd D
TD
Dohar
Joseph E
JE
Hebda
Patricia A
PA
D000818:Animals; D002245:Carbon Dioxide; D015232:Dinoprostone / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005931:Glottis / Q000293:injuries* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D053685:Laser Therapy / Q000009:adverse effects; D009092:Mucous Membrane / Q000293:injuries* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D014945:Wound Healing / Q000502:physiology*
D053583:Interleukin-1beta; D012333:RNA, Messenger; D002245:Carbon Dioxide; D015232:Dinoprostone