IL-1 Receptor Antagonist Inhibits Early Granulation Formation. 2016

Elizabeth A Nicolli, and Ankona Ghosh, and Sunny Haft, and Renee Frank, and Cecil James Saunders, and Noam Cohen, and Natasha Mirza
Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

OBJECTIVE Using a functional model of airway granulation tissue in laryngotracheal stenosis, we investigated changes in histopathology and inflammatory markers within granulation tissue in response to an interleukin-1 receptor antagonist (IL-1Ra). This study allows us to further delineate the immune response to wound healing and potentially identify treatment markers. METHODS Laryngotracheal complexes (LTCs) of donor mice underwent direct airway injury. The LTCs were transplanted into subcutaneous tissue of recipient mice in 2 groups: IL-1Ra treated and untreated. The IL-1Ra-treated arm received daily intraperitoneal injections of IL-1Ra for 3 weeks. The LTCs were then harvested. Granulation formation was measured. The mRNA expression of transforming growth factor (TGF) beta and IL-1 was quantified using real-time reverse transcript polymerase chain reaction. RESULTS There were statistically significant differences in lamina propria thickness. There were no statistically significant changes in mRNA expression of TGF-β and IL-1β between the treated and untreated specimens. CONCLUSIONS Using a previously described murine model, we delineate inflammatory markers that can be targeted for potential therapy. While the levels of inflammatory markers do not change significantly, the lamina propria thickness shows that the effects of IL-1 have been inhibited. The early use of the IL-1Ra will inhibit the efficacy of IL-1 in the inflammatory cascade and can prevent early granulation formation.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D007829 Laryngostenosis Developmental or acquired stricture or narrowing of the LARYNX. Symptoms of respiratory difficulty depend on the degree of laryngeal narrowing. Laryngeal Stenosis,Acquired Laryngeal Stenosis,Acquired Subglottic Stenosis,Congenital Subglottic Stenosis,Acquired Laryngeal Stenoses,Acquired Subglottic Stenoses,Congenital Subglottic Stenoses,Laryngeal Stenoses,Laryngeal Stenoses, Acquired,Laryngeal Stenosis, Acquired,Laryngostenoses,Stenoses, Acquired Laryngeal,Stenoses, Acquired Subglottic,Stenoses, Congenital Subglottic,Stenoses, Laryngeal,Stenosis, Acquired Laryngeal,Stenosis, Acquired Subglottic,Stenosis, Congenital Subglottic,Stenosis, Laryngeal,Subglottic Stenoses, Acquired,Subglottic Stenoses, Congenital,Subglottic Stenosis, Acquired,Subglottic Stenosis, Congenital
D007830 Larynx A tubular organ of VOICE production. It is located in the anterior neck, superior to the TRACHEA and inferior to the tongue and HYOID BONE. Anterior Commissure, Laryngeal,Anterior Commissure, Larynx,Laryngeal Anterior Commissure,Laryngeal Posterior Commissure,Posterior Commissure, Laryngeal,Posterior Commissure, Larynx,Anterior Commissures, Laryngeal,Anterior Commissures, Larynx,Commissure, Laryngeal Anterior,Commissure, Laryngeal Posterior,Commissure, Larynx Anterior,Commissure, Larynx Posterior,Commissures, Laryngeal Anterior,Commissures, Laryngeal Posterior,Commissures, Larynx Anterior,Commissures, Larynx Posterior,Laryngeal Anterior Commissures,Laryngeal Posterior Commissures,Larynx Anterior Commissure,Larynx Anterior Commissures,Larynx Posterior Commissure,Larynx Posterior Commissures,Posterior Commissures, Laryngeal,Posterior Commissures, Larynx
D006097 Granulation Tissue A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. Granulation Tissues,Tissue, Granulation,Tissues, Granulation
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014132 Trachea The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. Tracheas
D014135 Tracheal Stenosis A pathological narrowing of the TRACHEA. Stenoses, Tracheal,Stenosis, Tracheal,Tracheal Stenoses
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings
D016212 Transforming Growth Factor beta A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. Bone-Derived Transforming Growth Factor,Platelet Transforming Growth Factor,TGF-beta,Milk Growth Factor,TGFbeta,Bone Derived Transforming Growth Factor,Factor, Milk Growth,Growth Factor, Milk

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