PMID- 37759516
OWN - NLM
STAT- Publisher
LR  - 20231003
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 12
IP  - 18
DP  - 2023 Sep 16
TI  - Anti-Inflammatory Effects of Synthetic Peptides Based on Glucocorticoid-Induced 
      Leucine Zipper (GILZ) Protein for the Treatment of Inflammatory Bowel Diseases 
      (IBDs).
LID - 10.3390/cells12182294 [doi]
LID - 2294
AB  - Glucocorticoids (GCs) are commonly used to treat autoimmune and inflammatory 
      diseases, but their clinical effects and long-term use can lead to serious side 
      effects. New drugs that can replace GCs are needed. Glucocorticoid-induced 
      leucine zipper (GILZ) is induced by GCs and mediates many of their 
      anti-inflammatory effects, such as inhibiting the pro-inflammatory molecule 
      NF-kappaB. The GILZ C-terminal domain (PER region) is responsible for GILZ/p65NF-kappaB 
      interaction and consequent inhibition of its transcriptional activity. A set of 
      five short peptides spanning different parts of the PER region of GILZ protein 
      was designed, and their anti-inflammatory activity was tested, both in vitro and 
      in vivo. We tested the biological activity of GILZ peptides in human lymphocytic 
      and monocytic cell lines to evaluate their inhibitory effect on the 
      NF-kappaB-dependent expression of pro-inflammatory cytokines. Among the tested 
      peptides, the peptide named PEP-1 demonstrated the highest efficacy in inhibiting 
      cell activation in vitro. Subsequently, PEP-1 was further evaluated in two in 
      vivo experimental colitis models (chemically induced by DNBS administration and 
      spontaneous colitis induced in IL-10 knock-out (KO) mice (to assess its 
      effectiveness in counteracting inflammation. Results show that PEP-1 reduced 
      disease severity in both colitis models associated with reduced NF-kappaB 
      pro-inflammatory activity in colon lamina propria lymphocytes. This study 
      explored GILZ-based 'small peptides' potential efficacy in decreasing lymphocyte 
      activation and inflammation associated with experimental inflammatory bowel 
      diseases (IBDs). Small peptides have several advantages over the entire protein, 
      including higher selectivity, better stability, and bioavailability profile, and 
      are easy to synthesize and cost-effective. Thus, identifying active GILZ peptides 
      could represent a new class of drugs for treating IBD patients.
FAU - Paglialunga, Musetta
AU  - Paglialunga M
AUID- ORCID: 0000-0002-9133-8095
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
FAU - Flamini, Sara
AU  - Flamini S
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
FAU - Contini, Raffaele
AU  - Contini R
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
FAU - Febo, Marta
AU  - Febo M
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
FAU - Ricci, Erika
AU  - Ricci E
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
FAU - Ronchetti, Simona
AU  - Ronchetti S
AUID- ORCID: 0000-0002-5639-4243
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
FAU - Bereshchenko, Oxana
AU  - Bereshchenko O
AD  - Department of Philosophy, Social Sciences and Education, University of Perugia, 
      06123 Perugia, Italy.
FAU - Migliorati, Graziella
AU  - Migliorati G
AUID- ORCID: 0000-0002-9475-6399
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
FAU - Riccardi, Carlo
AU  - Riccardi C
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
FAU - Bruscoli, Stefano
AU  - Bruscoli S
AUID- ORCID: 0000-0003-0313-1615
AD  - Department of Medicine and Surgery, Section of Pharmacology, University of 
      Perugia, 06132 Perugia, Italy.
LA  - eng
GR  - 504854/CCF/CCF/United States
PT  - Journal Article
DEP - 20230916
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
SB  - IM
PMC - PMC10528232
OTO - NOTNLM
OT  - GILZ
OT  - IBDs
OT  - NF-kappaB
OT  - glucocorticoids
OT  - inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2023/09/28 06:43
MHDA- 2023/09/28 06:43
PMCR- 2023/09/16
CRDT- 2023/09/28 01:01
PHST- 2023/07/20 00:00 [received]
PHST- 2023/09/08 00:00 [revised]
PHST- 2023/09/14 00:00 [accepted]
PHST- 2023/09/28 06:43 [medline]
PHST- 2023/09/28 06:43 [pubmed]
PHST- 2023/09/28 01:01 [entrez]
PHST- 2023/09/16 00:00 [pmc-release]
AID - cells12182294 [pii]
AID - cells-12-02294 [pii]
AID - 10.3390/cells12182294 [doi]
PST - epublish
SO  - Cells. 2023 Sep 16;12(18):2294. doi: 10.3390/cells12182294.