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Use of il-22 in treating necrotizing enterocolitis

A technology of enterocolitis and IL-22, applied in the fields of biology and medicine, can solve the problems of reducing the morbidity and mortality of NEC

Active Publication Date: 2019-02-12
GENERON (SHANGHAI) CORP LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, current approaches to the prevention and treatment of NEC have failed to reduce the incidence and associated morbidity and mortality of NEC in neonates

Method used

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  • Use of il-22 in treating necrotizing enterocolitis
  • Use of il-22 in treating necrotizing enterocolitis
  • Use of il-22 in treating necrotizing enterocolitis

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0170] Preparation of IL-22, its dimers or multimers

[0171] IL-22, dimers or multimers thereof can be expressed using recombinant DNA techniques. Nucleotide sequences encoding IL-22 or IL-22 monomeric subunits can be inserted at restriction sites in replicable clones or protein expression vectors using known techniques. In some embodiments, a single nucleotide sequence encoding IL-22 or a monomeric subunit of IL-22 is inserted into a cloning or expression vector. In some embodiments, the nucleotide sequence encoding the IL-22 domain and the nucleotide sequence encoding the extended peptide region can be inserted into a cloning or expression vector, respectively, in such a way that when the nucleotide sequence is expressed as a protein , a continuous polypeptide is formed. In some embodiments, the nucleotide sequence encoding the linker, the nucleotide sequence encoding the dimerization domain, and the nucleotide sequence encoding the IL-22 domain, respectively, can be inse...

Embodiment 1

[0207] Example 1. Role of IL-22RA1 signaling in intestinal barrier maintenance.

[0208] IL-22RA1 (IL-22 receptor alpha 1 ) is a component of the IL-22 receptor, which is expressed on epithelial tissues.

[0209] By hybridizing IL-22RA1 fl / fl x villin-cre mice generate gut-specific IL22RA1 knockout mice (referred to herein as IL-22RA1 ΔIEC mice) to study the effect of IL-22RA1 signaling on the intestinal immune response.

[0210] Such as Figure 4 As shown, mice lacking intestinal IL-22RA1 signaling had significantly reduced numbers of goblet and Paneth cells in the small intestine compared with wild-type mice. Thus, IL-22RA1 signaling regulates the number of secretory cells in the small intestine.

[0211] Paneth cells are located at the bottom of the intestinal crypts, and they produce large amounts of antimicrobial peptides, such as lysozyme and Reg3g. Figure 5 Shown is the use against wild-type and IL-22RA1 ΔIEC Results of in situ hybridization experiments performe...

Embodiment 2

[0213] Example 2. IL-22 dimers protect intestinal epithelial cells from inflammation in vitro.

[0214] This example investigates the in vitro protective effect of exemplary IL-22 dimers on intestinal epithelial cells (IEC-6 cells) against inflammation. IL-22 dimers comprise two monomeric subunits, each comprising an IL-22 domain and an Fc domain (also referred to herein as "rIL-22"). An exemplary IL-22 dimer is composed of two monomeric subunits, each monomeric subunit comprising the amino acid sequence of SEQ ID NO:4.

[0215] The IEC-6 cells were subjected to the following four groups of conditions: (1) control group: IEC-6 cells were cultured in culture medium and not treated with IL-22 dimer or lipopolysaccharide (LPS); (2) LPS group: IEC-6 cells were cultured in medium, and then stimulated with LPS; (3) rIL-22 group: IEC-6 cells were pretreated with IL-22 dimer, and then cultured in medium; and ( 4) LPS+rIL-22 group: IEC-6 cells were pretreated with IL-22 dimer, and th...

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Abstract

The present invention relates to methods of preventing and / or treating necrotizing enterocolitis or other intestinal inflammations using an IL-22, a dimer or a multimer thereof.

Description

[0001] related application [0002] This application claims priority to US Provisional Patent Application No. 62 / 323,584, filed April 15, 2016, the contents of which are hereby incorporated by reference in their entirety. [0003] acknowledge government support [0004] This invention was made with government support under NIH Contract No. K06DK101608 awarded by the National Institutes of Health. The US Government has certain rights in this invention. [0005] Submit a sequence listing as an ASCII text file [0006] The contents of the following submitted ASCII text file are hereby incorporated by reference in their entirety: Computer Readable Form of the Sequence Listing (CRF) (File Name: 720622001340seqlist.TXT, Date of Record: April 14, 2017, Size: 22kb) . technical field [0007] The invention relates to the technical field of biology and medicine, in particular, the invention relates to the use of IL-22, its dimer or multimer in preventing and / or treating children's i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/20A61P1/00C07K14/54
CPCA61K38/20C07K14/54C07K2319/30A61P1/00A61K9/0019
Inventor J·K·考尔斯M·L·古德严孝强
Owner GENERON (SHANGHAI) CORP LTD
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