The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase
Background: Previous research has shown that type 1 interferons (IFN), such as IFN-α and IFN-ß, possess antiviral and antinociception effects. Elevated levels of microRNA-29a (miR-29a) have been observed during inflammatory pain, and as miR-29a targets the type 1 IFN receptor (IFNR1), our study aime...
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Elsevier
2025-03-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772609624001266 |
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| author | Chien-Cheng Liu Kuo-Chuan Hung Yu-Yu Li Eagle Yi-Kung Huang Chin-Chen Chu Lok-Hi Chow Ping-Heng Tan |
| author_facet | Chien-Cheng Liu Kuo-Chuan Hung Yu-Yu Li Eagle Yi-Kung Huang Chin-Chen Chu Lok-Hi Chow Ping-Heng Tan |
| author_sort | Chien-Cheng Liu |
| collection | DOAJ |
| description | Background: Previous research has shown that type 1 interferons (IFN), such as IFN-α and IFN-ß, possess antiviral and antinociception effects. Elevated levels of microRNA-29a (miR-29a) have been observed during inflammatory pain, and as miR-29a targets the type 1 IFN receptor (IFNR1), our study aimed to investigate the involvement of miR-29a, type 1 IFN, and IFNR1 in inflammatory pain. Methods: Inflammatory pain was induced in male rats using complete Freund's adjuvant (CFA). The changes in miR-29a, IFN-ß, and IFNR1 were measured on Days 2, 3, 5, 7, and 10 post-CFA injection and expression of IFNR1, phospho-ERK (phosphorylated extracellular signal-regulated kinase) (p-ERK), extracellular signal-regulated kinase (ERK), and IFN-stimulated gene 15 (ISG15) were measured in rats that received an miR-29a inhibitor or miR-29a mimic. Results: Our results demonstrated elevated miR-29a expression (CFA 3 days: mean difference [95% confidence interval, CI]: 0.860 [0.657–1.062]; CFA 5 days: mean difference [95% CI]: 1.120 [0.917–1.322], P<0.001, n=6) and decreased IFNR1 expression (CFA 3 days: mean difference [95% CI]: −0.300 [−0.470 to −0.130]; CFA 5 days: mean difference [95% CI]: −0.330 [−0.515 to −0.145], P=0.004, n=6) from Days 3–5 post-CFA induction, with IFN-ß expression showing a significant increase from Day 2 (F [3.30, 16.5]=34.3 for factor time, P≤0.01, n=6). Treatment with an miR-29a inhibitor alleviated CFA-induced mechanical allodynia and thermal hyperalgesia by Day 5 (P<0.001, n=9), concomitant with upregulation of IFNR1 and ISG15 expression, and downregulation of p-ERK (IFNR1; CFA 5 days + miR-29a inhibitor vs CFA 5 days; mean difference [95% CI]: 30.00 [20.31–39.69]; ISG15 conjugates; CFA 5 days + miR-29a inhibitor vs CFA 5 days, mean difference [95% CI]: 1.000 [0.9144–1.086]; free ISG15, mean difference [95% CI]: 2.402 [2.171–2.633]; p-ERK; CFA 5 days + miR-29a inhibitor vs CFA 5 days, mean difference [95% CI]: −32.00 [−34.10 to −29.90], P<0.001, n=9). Furthermore, in naïve rats, administration of an miR-29a mimic-induced mechanical allodynia, which was reversed by an ERK antagonist (P<0.001, n=6), associated with decreased IFNR1 and increased p-ERK expression (IFNR1; miR-29a mimic + dimethyl sulfoxide vs naïve; mean difference [95% CI]: −57.00 [−65.78 to −48.22]; miR-29a mimic + ASN007 vs naïve; mean difference [95% CI]: −60.00 [−71.00 to −49.00]. p-ERK; miR-29a mimic + dimethyl sulfoxide vs naïve, mean difference [95% CI]: 52.00 [47.01–56.99]; miR-29a mimic + ASN007 vs naïve, mean difference [95% CI]: 47.00 [42.51–51.49]; P<0.001, n=6). Conclusions: Inhibiting miR-29a expression attenuates inflammatory pain by modulating IFNR1, ISG15, and p-ERK expression, highlighting the interactive roles of miR-29a and IFN-ß in the regulation of inflammatory pain. |
| format | Article |
| id | doaj-art-56d4b33178f84e33ae2b0e25cad1f0a4 |
| institution | Kabale University |
| issn | 2772-6096 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | BJA Open |
| spelling | doaj-art-56d4b33178f84e33ae2b0e25cad1f0a42025-02-04T04:10:42ZengElsevierBJA Open2772-60962025-03-0113100376The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinaseChien-Cheng Liu0Kuo-Chuan Hung1Yu-Yu Li2Eagle Yi-Kung Huang3Chin-Chen Chu4Lok-Hi Chow5Ping-Heng Tan6Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung, TaiwanDepartment of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, TaiwanDepartment of Anesthesiology, Chi Mei Hospital, Chiali, Tainan, TaiwanDepartment of Pharmacology, National Defense Medical Center, Taipei, TaiwanDepartment of Anesthesiology, Chi Mei Medical Center, Tainan, TaiwanDepartment of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming Chiao-Tung University, School of Medicine, Taipei, Taiwan; Corresponding author. Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan.Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; Corresponding author. Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan.Background: Previous research has shown that type 1 interferons (IFN), such as IFN-α and IFN-ß, possess antiviral and antinociception effects. Elevated levels of microRNA-29a (miR-29a) have been observed during inflammatory pain, and as miR-29a targets the type 1 IFN receptor (IFNR1), our study aimed to investigate the involvement of miR-29a, type 1 IFN, and IFNR1 in inflammatory pain. Methods: Inflammatory pain was induced in male rats using complete Freund's adjuvant (CFA). The changes in miR-29a, IFN-ß, and IFNR1 were measured on Days 2, 3, 5, 7, and 10 post-CFA injection and expression of IFNR1, phospho-ERK (phosphorylated extracellular signal-regulated kinase) (p-ERK), extracellular signal-regulated kinase (ERK), and IFN-stimulated gene 15 (ISG15) were measured in rats that received an miR-29a inhibitor or miR-29a mimic. Results: Our results demonstrated elevated miR-29a expression (CFA 3 days: mean difference [95% confidence interval, CI]: 0.860 [0.657–1.062]; CFA 5 days: mean difference [95% CI]: 1.120 [0.917–1.322], P<0.001, n=6) and decreased IFNR1 expression (CFA 3 days: mean difference [95% CI]: −0.300 [−0.470 to −0.130]; CFA 5 days: mean difference [95% CI]: −0.330 [−0.515 to −0.145], P=0.004, n=6) from Days 3–5 post-CFA induction, with IFN-ß expression showing a significant increase from Day 2 (F [3.30, 16.5]=34.3 for factor time, P≤0.01, n=6). Treatment with an miR-29a inhibitor alleviated CFA-induced mechanical allodynia and thermal hyperalgesia by Day 5 (P<0.001, n=9), concomitant with upregulation of IFNR1 and ISG15 expression, and downregulation of p-ERK (IFNR1; CFA 5 days + miR-29a inhibitor vs CFA 5 days; mean difference [95% CI]: 30.00 [20.31–39.69]; ISG15 conjugates; CFA 5 days + miR-29a inhibitor vs CFA 5 days, mean difference [95% CI]: 1.000 [0.9144–1.086]; free ISG15, mean difference [95% CI]: 2.402 [2.171–2.633]; p-ERK; CFA 5 days + miR-29a inhibitor vs CFA 5 days, mean difference [95% CI]: −32.00 [−34.10 to −29.90], P<0.001, n=9). Furthermore, in naïve rats, administration of an miR-29a mimic-induced mechanical allodynia, which was reversed by an ERK antagonist (P<0.001, n=6), associated with decreased IFNR1 and increased p-ERK expression (IFNR1; miR-29a mimic + dimethyl sulfoxide vs naïve; mean difference [95% CI]: −57.00 [−65.78 to −48.22]; miR-29a mimic + ASN007 vs naïve; mean difference [95% CI]: −60.00 [−71.00 to −49.00]. p-ERK; miR-29a mimic + dimethyl sulfoxide vs naïve, mean difference [95% CI]: 52.00 [47.01–56.99]; miR-29a mimic + ASN007 vs naïve, mean difference [95% CI]: 47.00 [42.51–51.49]; P<0.001, n=6). Conclusions: Inhibiting miR-29a expression attenuates inflammatory pain by modulating IFNR1, ISG15, and p-ERK expression, highlighting the interactive roles of miR-29a and IFN-ß in the regulation of inflammatory pain.http://www.sciencedirect.com/science/article/pii/S2772609624001266IFN-βinflammatory paininterferon-stimulated gene 15microRNA 29atype 1 interferon receptor |
| spellingShingle | Chien-Cheng Liu Kuo-Chuan Hung Yu-Yu Li Eagle Yi-Kung Huang Chin-Chen Chu Lok-Hi Chow Ping-Heng Tan The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase BJA Open IFN-β inflammatory pain interferon-stimulated gene 15 microRNA 29a type 1 interferon receptor |
| title | The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase |
| title_full | The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase |
| title_fullStr | The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase |
| title_full_unstemmed | The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase |
| title_short | The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase |
| title_sort | concerted actions of microrna 29a and interferon β modulate complete freund s adjuvant induced inflammatory pain by regulating the expression of type 1 interferon receptor interferon stimulated gene 15 and p extracellular signal regulated kinase |
| topic | IFN-β inflammatory pain interferon-stimulated gene 15 microRNA 29a type 1 interferon receptor |
| url | http://www.sciencedirect.com/science/article/pii/S2772609624001266 |
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