Figure 1

Artemin increases locally in skin over long periods of time, whereas NGF shows a transient increase after peripheral inflammation. A-C: The NGF mRNA level almost doubled compared to the naïve level after 3 hours and sustained the same level until 12 hours, but returned to the normal level by 24 hours post CFA injection. In contrast, the artemin (ARTN) mRNA level showed a dramatic increase, more than doubling in 3 hours, and remained elevated until 7 days after injection (n = 4, mean ± SEM, ***p < 0.001, **p < 0.01, *p < 0.05, compared with naïve). D-S: ISHH for plantar skin revealed the source of NGF and artemin. NGF mRNA was expressed 3 hours after CFA injection (E, I) and it was expressed from the keratinocytes in the epidermis (G, arrows) and vascular smooth muscles in the dermis (K, arrows). Artemin mRNA was observed over a broad area of the epidermis 24 hours after CFA injection as seen in the dark-field photomicrograph (N and R). The artemin-generating cells were presumably keratinocytes in the epidermis (O, arrows) and eosin-labeled immune cells in the dermis according to the magnified bright-field microphotographs (S, arrows). Epi: epidermis, DM: dermis. Bars: 100 μm (D-F, H-J, L-N, P-R), 50 μm (G, K, O), 10 μm (S).