Statistical Analysis

To compare the cytokine concentrations in the serum at baseline, we used a one-way ANOVA and Tukey-Kramer HSD post-hoc tests to test for group differences. To compare the dynamics of cytokine concentration over time in serum and tissue, a ratio of the injured concentration mean to the uninjured concentration mean was calculated for each cytokine by group (Mm-UKY, Mm-Kenya, Mm-Wild, Ac and Ap) and time point (D1-D20). To normalize cytokine fold-change distributions, data were log transformed and tested for normality using a Shapiro-Wilk test and P-value > 0.05. A two-way ANOVA was then used to test for effects of time and group on tissue and serum separately. Pairwise comparisons were tested using the Tukey-Kramer HSD method. In the event that several undetected values existed at an individual timepoint and log transformed data still did not meet normality, we used non-parametric Wilcoxon rank sum tests with Steel Dwass post-hoc tests for pairwise comparisons. Datasets for which non-parametric analyses were performed are indicated in figure legends.

To compare the immunoblot data, pixel intensity was calculated for the bands of interest using an identical sized region of interest with ImageJ (51). The pixel intensity of pSTAT3 was normalized to ACTB and a two-way ANOVA with time and species was used to compare values and pairwise comparisons were made using the Tukey-Kramer HSD method. To compare the flow cytometry results, we used a two-way ANOVA with time and species on log-transformed data and pairwise comparisons were made using the Tukey-Kramer HSD method. To compare the ear-hole closure rate between control and celecoxib-treated animals we used a repeated-measures ANOVA and cubic regression, as previously published (41). To compare the ear-hole area and area of tissue positive for Picrosirius, we used a Student's t-test. All statistical tests were done using JMP Pro 14 (SAS Institute Inc., Cary, NC) or Prism 5.0 (GraphPad Software, Inc., San Diego, CA). A P-value < 0.05 was used to determine significance for each test. All graphs were created in Prism 5.0 and placed into figures using Illustrator CS5 (Adobe Systems, Inc. San Jose, CA).