Many cell types have been reported to produce RANTES including activated T lymphocytes, bronchial cells, fibroblasts, macrophages, and endothelial cells [52]. As shown in our study, AMs from mice pre-immunized with MP extracts plus alum are likely to be potent inducers of RANTES and MCP-1. Other factor such as vascular endothelial growth factor (VEGF) from small airway epithelial cells [53] and endothelial cells [54] might be a possible explanation for long-lasting

characteristics of MP pneumonia through angiogenesis and microvascular remodeling. It is still unknown why TLR-2 expression on AMs is up-regulated after intraperitoneal immunization of MP extracts plus alum. It is unlikely that circulating MP extracts directly stimulate AMs or their precursors in the alveolar spaces. In this regard, Fan et al. [55] reported that TLR-2 expression Forskolin chemical structure on selleck kinase inhibitor AMs was up-regulated through TLR-4 by shock-activated neutrophils in vivo and in vitro. Neutrophil NADPH

oxidase-derived oxidants signaling mediates the TLR-2–TLR-4 cross talk both in endothelial cells and in AMs, which results in the activation of positive feedback signals against invading pathogens. The present study highlights distinct reaction to IT between mice with and without pre-immunization of MP extracts. Our results suggest that subclinical or preceding MP infection may greatly influence the degree of inflammation in MP pneumonia. Unraveling the mechanisms by which cAMP innate immunity regulates cytokine/chemokine expression will significantly

improve our understanding of the pathogenesis of MP and will help to develop novel therapeutic strategies to control mycoplasma associated infections in humans. The authors declare that they have no competing interests. TS and both KN conducted the design of the study and had a major role in drafting the manuscript. TS carried out the experiments and the preliminary data analyses. NM helped in conducting the pretreatments and performing the experiments. YF, KI and TO participated in the pathological evaluation. DK, HW, HI, HT, SK and HG participated in the design of the study and interpretation of the experimental findings. All authors read and approved the final manuscript. This work was supported by Grant-in-aid from Scientific Research (19590911). We are very grateful to Dr. Fusayo Adachi. Institute of Medical Science, The University of Tokyo, for their valuable contribution and to Akiko Kitazawa, Kyorin University School for providing technical assistance. “
“The normal development of B lymphocytes requires various transcription factors, including E2A [1], EBF1 [2], Pax5 [3], PU.1 [4], Ikaros family proteins [5] and [6] and so on [7] and [8].