Inflammasomes: Clinical and Therapeutic Implications

404 Pages·2018·7.916 MB·English

by  Mario D. Cordero, Elísabet Alcocer-Gómez

Experientia Supplementum 108
Mario D. Cordero 
Elísabet Alcocer-Gómez E ditors
Infl ammasomes:
Clinical and
Therapeutic
Implications
Experientia Supplementum
Volume 108
Moreinformationaboutthisseriesathttp://www.springer.com/series/4822
(cid:129)
Mario D. Cordero Elísabet Alcocer-Gómez
Editors
fl
In ammasomes: Clinical
and Therapeutic Implications
Editors
MarioD.Cordero ElísabetAlcocer-Gómez
DepartmentofPhysiology DepartamentodePsicologíaExperimental
InstituteofNutritionandFoodTechnology FacultaddePsicología
“JoséMataix”,BiomedicalResearch UniversidaddeSevilla
Center(CIBM),UniversityofGranada Seville,Spain
Armilla,Spain
ISSN1664-431X ISSN2504-3692 (electronic)
ExperientiaSupplementum
ISBN978-3-319-89389-1 ISBN978-3-319-89390-7 (eBook)
https://doi.org/10.1007/978-3-319-89390-7
LibraryofCongressControlNumber:2018951069
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Acknowledgments
Theeditorswanttothankalltheauthorsforthetremendouseffortanddedicationto
thedevelopmentofthisbookaswellasthehighlevelofchapters.
v
Contents
1 InflammasomesinClinicalPractice:ABriefIntroduction. . . . . . . . 1
ElísabetAlcocer-Gómez,BeatrizCastejón-Vega,
MacarenaLópez-Sánchez,andMarioD.Cordero
2 TheInflammasomesinCardiovascularDisease. . . . . . . . . . . . . . . . 9
GerardusP.J.vanHoutandLenaBosch
3 InflammasomesinCNSDiseases. . . . . . . . . . . . . . . . . . . . . . . . . . . 41
EduardoA.Albornoz,TrentM.Woodruff,andRichardGordon
4 LungDiseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
SaleelaM.Ruwanpura,SarahRosli,andMichelleD.Tate
5 TraumaticInjury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
BornaReljaandJohann-PhilippHorstmann
6 InflammasomeinthePathogenesisofPulmonaryDiseases. . . . . . . 111
FengyingXu,ZongmeiWen,XueyingShi,andJieFan
7 InflammasomeandOralDiseases. . . . . . . . . . . . . . . . . . . . . . . . . . 153
PedroBullon,LuisE.Pavillard,andRafaeldelaTorre-Torres
8 InflammasomesintheKidney. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
HollyL.Hutton,MalihaA.Alikhan,andA.RichardKitching
9 Pro-InflammatoryActionsofRedBloodCell-DerivedDAMPs. . . . 211
ViktóriaJeney
10 RoleofInflammasomesintheDevelopmentofGastrointestinal
Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
MazharA.Kanak,YoshitaroShindo,PavithraSaiKumar,
andBashooNaziruddin
11 InflammasomesinBoneDiseases. . . . . . . . . . . . . . . . . . . . . . . . . . . 269
GabrielMbalavieleandDeborahJ.Veis
vii
viii Contents
12 InflammasomeandCancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
ZhiyuWang,NengWang,YifengZheng,andShengqiWang
13 AgingandtheInflammasomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
FabiolaMarín-Aguilar,JesúsRuiz-Cabello,andMarioD.Cordero
14 GeneticsofInflammasomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
WanessaCardosodaSilva,EdioneC.Reis,TelmaM.Oshiro,
andAlessandraPontillo
15 InhibitingInflammasomeswithSmallMolecules. . . . . . . . . . . . . . . 343
AvrilA.B.Robertson
Chapter 1
fl
In ammasomes in Clinical Practice: A Brief
Introduction
ElísabetAlcocer-Gómez,BeatrizCastejón-Vega,MacarenaLópez-Sánchez,
andMarioD.Cordero
Contents
1.1 Introduction.................................................................................. 2
1.2 ClinicalAspect............................................................................... 4
1.2.1 DiagnosticTools..................................................................... 5
1.2.2 PharmacologicalTreatments......................................................... 6
1.3 Conclusions.................................................................................. 7
References.......................................................................................... 7
Abstract Inflammasomes are multiprotein complexes formed and activated after
exposuretopathogenicmicrobesandhostdangersignalsthatcontrolthematuration
and production of IL-1β and IL-18. Their implication in different diseases such as
cardiovascular,neurodegenerative,psychiatric,andmetabolicdiseasesopensadoor
to developing new therapeutic perspectives. However, the rapid increase in the
E.Alcocer-Gómez(*)
DepartamentodePsicologíaExperimental,FacultaddePsicología,UniversidaddeSevilla,
Sevilla,Spain
B.Castejón-Vega
DepartamentodePsicologíaExperimental,FacultaddePsicología,UniversityofSevilla,
Sevilla,Spain
ResearchLaboratory,OralMedicineDepartment,UniversityofSevilla,Sevilla,Spain
M.López-Sánchez
ResearchLaboratory,OralMedicineDepartment,UniversityofSevilla,Sevilla,Spain
CentroAndaluzdeBiologíadelDesarrollo(CABD),UniversidadPablodeOlavide-CSIC-Junta
deAndalucía,Sevilla,Spain
M.D.Cordero(*)
CentroAndaluzdeBiologíadelDesarrollo(CABD),UniversidadPablodeOlavide-CSIC-Junta
deAndalucía,Sevilla,Spain
DepartmentofPhysiology,InstituteofNutritionandFoodTechnology“JoséMataix”,
BiomedicalResearchCenter(CIBM),UniversityofGranada,Armilla,Spain
e-mail:[email protected]
©SpringerInternationalPublishingAG,partofSpringerNature2018 1
M.D.Cordero,E.Alcocer-Gómez(eds.),Inflammasomes:ClinicalandTherapeutic
Implications,ExperientiaSupplementum108,
https://doi.org/10.1007/978-3-319-89390-7_1
2 E.Alcocer-Gómezetal.
knowledge about inflammasomes is associated with their involvement in clinical
practice.Twotopicsopenthewaytofuturelinesofresearch:aclinicaltrialwiththe
newspecificinhibitorsandthedevelopmentofdiagnostictools.
Keywords Inflammasomes·NLRP3·Clinicalmedicine·Diagnosis·
Pharmacologicaltreatment
1.1 Introduction
Theaimofmedicineandclinicalresearchistounderstandthebiologicalprocesses
of health and thedevelopment of tools for the treatmentand diagnosis of diseases.
Thus,weneedabalancebetweenbasicandclinicalresearchinatranslationalform.
Differentexamplesofthisarethedevelopmentofdrugsanddiagnosticmethodsfor
theidentificationofmolecularpathwaysandtargetsinvolvedinthepathophysiology
ofthediseases.
Fordecades,inflammationhasbeenthefocusofresearchers’attentionbecauseof
itsdirectandindirectparticipationinthepathophysiologyofmanydiseases.Froman
immunity viewpoint, after an infection, microorganisms are initially sensed by
pattern-recognition receptors (PRRs) of the innate immune system. These PRRs
areexpressedinvariousimmunecellssuchasmacrophages,dendriticcells,epithe-
lialcells,neutrophils,andadaptiveimmunecells.TheToll-likereceptors(TLRs),a
particular type of PRRs, are expressed on the cell membrane surface and can be
activated by different external signals with a pathogen profile known as pathogen-
associated molecular patterns (PAMPs). The PRRs can also be triggered during
sterile inflammatory diseases, in the absence of microbes, by different damaging
profiles,suggestingthecrucialroleofdangersignalsthatarehost-derived,andthat
areknownasdanger-associatedmolecularpatterns(DAMPs).PAMPsandDAMPs
can also trespass on the plasma membrane and trigger intracellular innate immune
receptorsdirectly,forexample,viarecognitionofDNAorRNAinthecytoplasm.In
thelossofhomeostasisconditions,somecytosolicinnateimmunesensorscanalso
be indirectly activated. Among these sensors are included NOD-like receptors or
nucleotide-binding oligomerization domain-like receptors (NLRs) that possess a
pyrin domain (PYD) or caspase activation and recruitment domain (CARD) in
their N-terminal regions, which have partial homology in man and mouse
(Fig.1.1a)andwhichhavespecificligands(Fig.1.1b).Ofthese,theNLRP3isthe
best described, which are composed of a carboxy-terminal LRR domain, a central
NACHT and NAD domain (NBD), and an amino-terminal PYD (Fig. 1.2a)
(Lamkanfi and Dixit 2014), with a similar structure between humans and the
mouse, both the most studied species with regard to inflammasomes (Fig. 1.2b).
Afteranassemblystimulus,NLRisassociatedwiththeadaptermoleculeapoptosis-
associatedspeck-likeproteinthatcontainsaCARDdomain(ASD)intheN-terminal
regions, and the effector protein caspase-1 (Fig. 1.3a), and forms the named
inflammasome complex (Lamkanfi and Dixit 2014). These inflammasome com-
plexes regulate the activation of caspase-1, which in turn regulates the cleavage of
cytokines interleukin-1beta (IL-1β) and interleukin-18 (IL-18). The NLRP3