ABSTRACT
The aim of the present study was to explore the specific pattern of brain deactivation elicited by painful stimuli, in contrast with that elicited by tactile stimuli. Functional magnetic resonance imaging (fMRI) data were collected from 62 healthy subjects under painful and tactile stimuli with varying intensities. The brain deactivations under different conditions were identified using the general linear model. Two-way analysis of variance (ANOVA) was performed to test whether there was a significant interaction between perceived stimulus intensity (factor 1: high intensity, low intensity) and stimulus modality (factor 2: pain, touch) on the brain deactivations. The results showed that there were significant interactions between stimulus intensity and stimulus modality on the deactivations of left medial superior frontal gyrus, left middle occipital gyrus, left superior frontal gyrus and right middle occipital gyrus (P < 0.05, Cluster-level FWE). The deactivations induced by painful stimuli with low perceived intensity (β = -3.38 ± 0.52) were significantly stronger than those induced by painful stimuli with high perceived intensity (β = -1.22 ± 0.54) (P < 0.001), whereas the differences between the deactivations induced by tactile stimuli with different perceived intensities were not statistically significant. In addition, there were no significant differences between the deactivations elicited by painful and tactile stimuli with the same stimulus intensities. These results suggest that there is a specific relationship between the deactivations induced by painful stimuli in multiple brain regions (such as the left medial superior frontal gyrus) and the stimulus intensity, providing evidence for a deeper understanding of the brain mechanisms underlying pain perception.
Subject(s)
Humans , Touch/physiology , Physical Stimulation/methods , Pain , Brain/physiology , Magnetic Resonance Imaging/methods , Brain MappingABSTRACT
Objective • To investigate the role and the regulation mechanism of SUMOylation of peroxisome proliferator activated receptor γ1 (PPARγ1) in macrophage M2 polarization induced by interleukin-4 (IL-4). Methods • To investigate the SUMOylation of PPARγ1 and identify its SUMOylated site, immunoprecipitation (IP) with anti-FLAG/HA antibody and Western blotting were used after plasmids FLAG-PPARγ1-WT/mutant and HA-SUMO1 being co-transfected into HEK293T cells. To determine SENP1 can de-SUMOylate PPARγ1, IP was used when HEK293T cells were co-transfected by FLAG-PPARγ1-WT, HA-SUMO1 and RGS-SENP1-WT, or SENP1 mutant plasmids. The change of the endogenous SUMOylation of PPARγ1 during M2 polarization was checked by IP and Western blotting by using PPARγ or SUMO1 antibodies in cell lysates of RAW264.7 cells and primary peritoneal macrophages induced by IL-4. The expression of some M2 related marker genes were detected by real-time quantitative polymerase chain reaction in PPARγ1-WT/mutants stably-overexpressed RAW264.7 cells. Chromatin immunoprecipitation (ChIP) experiment was used to confirm the different ability of binding to the promoter of arginase (Arg1) between PPARγ1-WT and PPARγ1-K77R. Results • It has been identified that the major SUMOylated site of PPARγ1 was Lys77, which could be de-SUMOylated by SENP1. The endogenous SUMOylation of PPARγ1 decreased when macrophage polarized to M2 macrophage induced by IL-4. The expression of Arg1 increased in PPARγ1-K77R stably-overexpressed RAW264.7 cells. PPARγ1-K77R easily bound to the promoter of Arg1 gene, showing more transcription activity. Conclusion • De-SUMOylation of PPARγ1 at Lys77 can enhance its transcription activity by promoting the expression of Arg1 gene, which is involved in the regulation of macrophage M2 polarization.
