Referee 2's review:

Summary:
The authors describe the pathology and expression changes associated with ventilator induced lung injury. The influence of the MAPK pathway on this mechanism was highlighted by the use of jnk-/- and mkk3-/- mice as modulators of the severity of key indicators of this injury such as apoptosis, and the presence of neutrophils and total protein in BALF. This study also utilizes microarray analysis to profile expression changes in parallel with the above measures.

Overall this is a well designed study that has identified of several genes, particularly mmp8 that may contribute to aspects VILI.

Comments:
The first page of Table S1 has some formatting issues and is not legible. BALF should be defined at its first occurrence in the methods on page 6. It is stated that gene lists with FDR correction were used for generation of the heatmap and a list without FDR correction was used for discovery of functional groups. Clarify the figure legend to Table S1 to explain which data set is presented here. The Real time PCR was normalized to B-glucuronidase. While this has been used as a reference gene in other published RT-PCR studies it is not exceedingly common. Explain why this reference gene was chosen over more common “housekeeping” genes such as B-Actin, GapDH, Ribosomal proteins, etc.

Table 1 is largely redundant given the data presented in figures 1 and 2. Additionally
Table 2 does not contribute greatly to the understanding of this study. Both tables should be moved to supplementary data.

Figure 4 should present the immunoblots alongside the quantitated bar graphs.
Figure 8 – It is noted in the text that GADD45-alpha is primarily a nuclear protein and that after ventilation increased staining was observed. From the presented images this does not appear to be the case, with the nuclear content of GADD45-alpha appearing similar in panel A and B. Cytoplasmic staining does appear to be higher in panel B, if this was the authors intention, then the text should be altered to make this obvious. As this is the only figure to address whether the mRNA changes are reflected at the protein level quantiation must accompany this figure for both GADD45-alpha and MMP8, either with cell counts or a new figure with a western blot.

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.