Treatment of inflammatory diseases

a technology for inflammatory diseases and diseases, applied in the field of inflammatory diseases, can solve the problems of increased potential for tissue injury, illness or disease, and inability to regulate the inflammatory respons

Inactive Publication Date: 2018-11-29
JACKSON LAB THE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0019]In certain embodiments, the method further comprises: d) contacting a second population of test cells with the pro-inflammatory cytokine, and determining the effect thereon of inhibiting a function of the one or more genes, wherein the one or more genes are identified as pro-inflammatory if at least one inflammatory phenotype induced by the pro-inflammatory cytokine is allevia...

Problems solved by technology

In some cases, however, the inflammatory response cannot be regulated and the potential for tissue injury is increased.
Depending on the type of environmental exposure, genetic predisposition, and a variety of ill-defined factors, abnormally large numbers of inflammatory cells can be recruited at different sites of the respiratory system, resulting in illness or dise...

Method used

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  • Treatment of inflammatory diseases
  • Treatment of inflammatory diseases
  • Treatment of inflammatory diseases

Examples

Experimental program
Comparison scheme
Effect test

example 1

f Human Airway Stem Cells

[0606]Human (upper) airway stem cells can be isolated and clonally expanded according to the method described in the co-pending co-owned application filed on the same day (Mar. 15, 2013), entitled “Isolation of Non-Embryonic Stem Cells and Uses Thereof,” as U.S. Provisional Application No. 61 / 792,027 (incorporated herein by reference). Also see Section 2 above.

[0607]In this experiment, human airway biopsy was digested with 2 mg / mL collagenase type IV (Gibco, cat. no. 17104-109), and epithelial cells were isolated and cultivated onto a feeder layer of lethally irradiated 3T3-J2 cells (originally from the Howard Green laboratory of Harvard Medical School, Boston, Mass.) in CFAD media based on the previously described methods for epidermal stem cells and airway epithelial stem cells (see Barrandon and Green, Proc. Natl. Acad. Sci. USA 84:2302-2306, 1987; Kumar et al., Cell 147:525-538, 2011; Senoo et al. 2007, Cell 129:523-536). CFAD culture medium contains thr...

example 2

Methods Using Sensitized Test Cells from an Asthma Patient

[0608]Upper airway stem cells were isolated using the methods of the invention from an asthma patient. Microarray analysis revealed that, without IL-13 treatment, in about 13 days, normal upper airway stem cells differentiate into both ciliated cells and goblet cells. However, Asthma patient stem cells have extremely limited or no ability to form ciliated cells. Based on the microarray data, AMTN expression in the patient cells was already 35-fold lower, and TCN1 expression in the patient was already 45-fold higher compared to normal control at day 13. Consistently with this observation, Asthma stem cells were more susceptible to IL-13 treatment, and gave rise to goblet cell metaplasia much faster and stronger than normal upper airway epithelial stem cells. See FIG. 19.

[0609]Note that on Day 15, without IL-13 treatment, normal upper airway stem cells differentiate into both goblet cells and ciliated cells. IL-13 treatment led...

example 3

Differentiation Assays for Human and Rat Cells

[0612]Air-liquid interface culture of upper airway epithelial cells was performed as described (Schmidt et al., Toxicol. Lett. 88:75-79, 1996; Kumar et al, supra, both incorporated by reference). Briefly, upper airway stem cells were cultured on Transwell plates (Corning) coated with irradiated 3T3-J2 feeder cells in the presence of CFAD medium (a base medium). At confluence, the medium on the inserts was removed and the medium outside the insert was changed to differentiation medium (DMEM / F12 1:1, 50 mg / mL penicillin; 50 mg / mL streptomycin; Fungizone 2.5 mg / mL (GIBCO); 10 ng / mL cholera toxin, retinoic acid 10−7 M; 10% Knockout SR serum replacement (GIBCO)).

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Abstract

The invention described herein relates to methods of screening for pro-inflammatory genes and anti-inflammatory genes which may be useful for treating an inflammatory disease, disorder, or otherwise abnormal condition, such as an inflammatory lung disease. The identified pro-inflammatory genes and anti-inflammatory genes may be used to produce pharmaceutical compositions for use in treating the inflammatory disease, disorder, or otherwise abnormal condition.

Description

REFERENCE TO RELATED APPLICATION[0001]This Application is a Divisional of application Ser. No. 14 / 853,192 filed on Sep. 14, 2015 which is a continuation application of International Application No. PCT / US2014 / 025776, filed on Mar. 13, 2014, which claims the benefit of the filing date, under 35 U.S.C. § 119(e), of U.S. Provisional Application Nos. 61 / 793,110 and 61 / 788,602, both filed on Mar. 15, 2013, the entire contents of each of which are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]Humans breath more than one cubic meter of air every hour, and the large quantities of particles, antigens, infectious agents and toxic gases and fumes that are present in inhaled air are usually dealt with by the lung. The interaction of these particles with the immune system and other lung defense mechanisms results in the generation of a controlled inflammatory response which is usually protective and beneficial. In general, this process regulates itself in order to preserve th...

Claims

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Application Information

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IPC IPC(8): G01N33/50C12N15/113C12Q1/6883A61K38/17C07K16/18
CPCG01N33/5023C12N2320/30C12N15/113C12Q1/6883A61K38/17C12Q2600/158C07K16/18
Inventor XIAN, WA
Owner JACKSON LAB THE
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