IL-1α Counteract TGF-ß Regulated Genes and Pathways in Human Fibroblasts.

Dysregulated wound healing is commonly associated with excessive fibrosis. Connective tissue growth factor (CTGF/CCN2) is characteristically overexpressed in fibrotic diseases and stimulated by transforming growth factor-ß (TGF-ß) in dermal fibroblasts. We previously showed that interleukin-1 (IL-1α) counteracts TGF-ß-stimulated CTGF mRNA and protein expression in these cells. The aim of this study was to explore the effects of IL-1α on further genes and pathways in TGF-ß regulated fibroblasts. Transcriptional microarray and multiple comparison analysis showed that the antagonizing effects of IL-1α was much more prominent than the synergistic effects, both with respect to number of genes and extent of changes in gene expression. Moreover, comparing canonical pathways by gene set enrichment analysis and the Ingenuity Pathway Analysis tool revealed that IL-1α counteracted TGF-ß in the top six most confident pathways regulated by both cytokines. Interferon and IL-1 signaling, as well as two pathways involved in apoptosis signaling were suppressed by TGF-ß and activated by IL-1α. Pathways involving actin remodeling and focal adhesion dynamics were activated by TGF-ß and suppressed by IL-1α. Analyzing upstream regulators in part corroborate the comparison of canonical pathways and added cell cycle regulators as another functional group regulated by IL-1α. Finally, gene set enrichment analysis of fibrosis-related genes indicated that IL-1 moderately counteracts the collective effect of TGF-ß on these genes. Microarray results were validated by qPCR. Taken together, the results indicate prominent antagonistic effects of IL-1α on TGF-ß regulated interferon signaling, as well as on a wide variety of other genes and pathways in fibroblasts. J. Cell. Biochem. 117: 1622-1632, 2016. © 2015 Wiley Periodicals, Inc.

Stimulation of adrenergic ß-receptors enhances mydriasis in a porcine eye model.

PURPOSE: To compare the mydriatic effect of intracamerally injected isoprenaline plus phenylephrine to phenylephrine alone and to epinephrine in a porcine eye model, aiming to eventually find the best combination of adrenergic substances for surgical mydriasis in humans. METHODS: In this study, we used 89 intact eyes from newly slaughtered pigs, pretreated with 2.0 mg of intracameral acetylcholine. After waiting 60 seconds for miosis to develop, 0.15 ml 0.3% isoprenaline and 0.15 ml 3.0% phenylephrine were injected sequentially with a 90-second interval in 21 eyes. In another 22 eyes, the same substances were given in the reverse order. In 20 eyes, 0.15 ml of 0.025% epinephrine was injected, and as a negative control 0.15 ml of balanced salt solution was injected in 26 eyes. The pupils were filmed during the treatments, and the mean pupil diameters were measured every 15 seconds from the video recordings. RESULTS: Phenylephrine injected after isoprenaline had a larger mydriatic effect than epinephrine (p < 0.01). Without isoprenaline pretreatment, the mydriatic effect of phenylephrine was significantly smaller than that of epinephrine (p < 0.05). Isoprenaline also exhibited a small mydriatic effect of its own. CONCLUSIONS: The ß-receptor stimulator isoprenaline enhances the mydriatic effect of intracameral phenylephrine, indicating a role for the ß-receptor in the mydriatic response. Mydriasis mediated by ß-receptors may explain why nonspecific adrenergic stimulators such as epinine and epinephrine can have larger mydriatic effects than the specific α(1)-receptor stimulator phenylephrine.

Spatial distribution of corneal light scattering after corneal collagen crosslinking.

PURPOSE: To assess the spatial distribution and time course of increased corneal light scattering after corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A irradiation. SETTING: Umeå University Hospital Eye Clinic, Umeå, Sweden. DESIGN: Case series. METHODS: Eyes with keratoconus were examined with Scheimpflug photography before and 1 and 6 months after CXL. Corneal light scattering was quantified throughout the corneal thickness at 8 measurement points 0.0 to 3.0 mm from the central cornea. RESULTS: The study comprised 11 eyes of 11 patients. Central corneal light scattering increased significantly 1 month after CXL (P<.001). At 6 months, it decreased (P = .002); however, it was still higher than pretreatment values (P<.001). Light scattering at 1 month was more pronounced in the superficial stroma, gradually diminishing to zero at 240 µm depth. It was greater at the corneal center than 1.0 to 3.0 mm from the center. At 6 months, a second peak of light scattering occurred between 240 µm and 340 µm depth. No increased light scattering deeper than 340 µm was seen at either time point. CONCLUSIONS: Corneal light scattering after CXL showed distinctive spatial and temporal profiles. Analysis of corneal light scattering may give an impression of tissue changes, the depth of the CXL treatment effect, and the corneal response to the treatment. Scheimpflug photography appears to be useful for this purpose. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.